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Biomedicines
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Cardiovascular and Metabolic Disease: New Treatment and Future Directions
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Cardiovascular and Metabolic Disease: New Treatment and Future Directions

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 47306

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Alfredo Caturano

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Guest Editor
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: cardiovascular pharmacology; diabetes pharmacology; brugada syndrome; NAFLD; cardiovascular risk
Special Issues, Collections and Topics in MDPI journals
Dr. Raffaele Galiero

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Guest Editor
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy
Interests: diabetes; peripheral neuropathy; microangiopathy; cardiovascular disease (CVD)

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In 2019, it has been estimated that 17.9 million people died from CVDs (32% of all global deaths). Of these deaths, 85% were due to heart attack and stroke. These data are usually powered by the coexistence of metabolic diseases, in particular diabetes. In fact, about 422 million people worldwide have diabetes, the majority living in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. It is vital to detect CVDs and metabolic disease as early as possible, as most cases can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity, and harmful use of alcohol. Moreover, we are the main actors and observers of the innovations in every field of CVDs and metabolic disease treatment, from the pharmacological approach, with the advent of sodium glucose cotransporter 2 inhibitors for both heart failure and diabetes, to the improvement of new less-invasive and invasive techniques such as immediate revascularization in both heart and brain infarction and new methods of mechanical cardiac support and multiorgan transplantation for the most advanced forms of heart failure.

Given the complexity of this topic and its impact on clinical practice and public health, Biomedicines is launching a Special Issue entitled “Cardiovascular and Metabolic Disease: New Treatments and Future Directions” with the aim of gathering accurate and up-to-date scientific information on all aspects of new and upcoming treatment opportunities for CVDs and metabolic diseases. It is my privilege to invite you and your co-workers to share their experience and expertise by submitting original research articles, systematic reviews and review articles reporting new ideas and recent advances in this topic.

Dr. Alfredo Caturano
Dr. Raffaele Galiero
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiovascular disease
  • metabolic disease
  • diabetes
  • therapy
  • drugs
  • implantable device
  • heart failure
  • heart transplantation
  • cardiac surgery
  • future directions

 

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Published Papers (13 papers)

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Research

Jump to: Review

18 pages, 792 KiB  
Article
The Impact of SGLT2 Inhibitor Dapagliflozin on Adropin Serum Levels in Men and Women with Type 2 Diabetes Mellitus and Chronic Heart Failure
by Alexander A. Berezin, Zeljko Obradovic, Ivan M. Fushtey, Tetiana A. Berezina, Evgen V. Novikov, Lukas Schmidbauer, Michael Lichtenauer and Alexander E. Berezin
Biomedicines 2023, 11(2), 457; https://doi.org/10.3390/biomedicines11020457 - 4 Feb 2023
Cited by 9 | Viewed by 3158
Abstract
Background: adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium–glucose [...] Read more.
Background: adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium–glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin might represent cardiac protective effects in T2DM patients with known chronic HF through the modulation of adropin levels. Methods: we prospectively enrolled 417 patients with T2DM and HF from an entire cohort of 612 T2DM patients. All eligible patients were treated with the recommended guided HF therapy according to their HF phenotypes, including SGLT2 inhibitor dapagliflozin 10 mg, daily, orally. Anthropometry, clinical data, echocardiography/Doppler examinations, and measurements of biomarkers were performed at the baseline and over a 6-month interval of SGLT2 inhibitor administration. Results: in the entire group, dapagliflozin led to an increase in adropin levels by up to 26.6% over 6 months. In the female subgroup, the relative growth (Δ%) of adropin concentrations was sufficiently higher (Δ% = 35.6%) than that in the male subgroup (Δ% = 22.7%). A multivariate linear regression analysis of the entire group showed that the relative changes (Δ) in the left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e’ were significantly associated with increased adropin levels. In the female subgroup, but not in the male subgroup, ΔLVEF (p = 0.046), ΔLAVI (p = 0.001), and ΔE/e’ (p = 0.001) were independent predictive values for adropin changes. Conclusion: the levels of adropin seem to be a predictor for the favorable modification of hemodynamic performances during SGLT2 inhibition, independent ofN-terminal brain natriuretic pro-peptide levels. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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10 pages, 1720 KiB  
Article
Effects of a Combination of Empagliflozin Plus Metformin vs. Metformin Monotherapy on NAFLD Progression in Type 2 Diabetes: The IMAGIN Pilot Study
by Alfredo Caturano, Raffaele Galiero, Giuseppe Loffredo, Erica Vetrano, Giulia Medicamento, Carlo Acierno, Luca Rinaldi, Aldo Marrone, Teresa Salvatore, Marcellino Monda, Celestino Sardu, Raffaele Marfella and Ferdinando Carlo Sasso
Biomedicines 2023, 11(2), 322; https://doi.org/10.3390/biomedicines11020322 - 23 Jan 2023
Cited by 21 | Viewed by 3449
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a heterogeneous group of metabolic liver diseases and is characterized by the presence of steatosis in at least 5% of hepatocytes. The aim of our study was to assess the effect of the combination therapy of empagliflozin [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) comprises a heterogeneous group of metabolic liver diseases and is characterized by the presence of steatosis in at least 5% of hepatocytes. The aim of our study was to assess the effect of the combination therapy of empagliflozin + metformin vs. metformin monotherapy on NAFLD progression in type 2 diabetic (T2DM) patients. Sixty-three metformin-treated T2DM patients who were SGLT2i-naïve and had an ultrasound diagnosis of NAFLD (aged 60.95 ± 11.14 years; males, 57.1%) were included in the present analysis. Thirty-three started the combination therapy. All patients were observed for 6 months and routinely monitored with anthropometry, blood biochemistry, and FibroScan®/CAP. At the 6-month follow-up, the combination therapy group presented a significant reduction in BMI (30.83 ± 3.5 vs. 28.48 ± 3.25), glycated hemoglobin (8.2 (7.4–8.8)) vs. 7.2 (6.8–7.9), ALT (68.5 (41.5–88.0) vs. 45.00 (38.00, 48.00)), CAP parameter (293.5 (270.0–319.25) vs. 267.00 (259.50, 283.75)) and steatosis degree (p = 0.001) in comparison with the control group, whose parameters remained almost stable over time. In patients affected by T2DM, the combination of empagliflozin + metformin vs. metformin monotherapy ameliorated liver steatosis, ALT levels, body weight, and glycated hemoglobin after a 6-month follow-up. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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11 pages, 1160 KiB  
Article
Relationship between Arterial Calcifications on Mammograms and Cardiovascular Events: A Twenty-Three Year Follow-Up Retrospective Cohort Study
by Natalia González Galiano, Noemi Eiro, Arancha Martín, Oscar Fernández-Guinea, Covadonga del Blanco Martínez and Francisco J. Vizoso
Biomedicines 2022, 10(12), 3227; https://doi.org/10.3390/biomedicines10123227 - 12 Dec 2022
Cited by 6 | Viewed by 2106
Abstract
Purpose: Breast arterial calcifications (BAC) have been associated with cardiovascular diseases. We aimed to examine whether the presence of BAC could predict the development of cardiovascular events in the very long term, as evidence has suggested. Patients and Methods: We conducted a 23-year [...] Read more.
Purpose: Breast arterial calcifications (BAC) have been associated with cardiovascular diseases. We aimed to examine whether the presence of BAC could predict the development of cardiovascular events in the very long term, as evidence has suggested. Patients and Methods: We conducted a 23-year follow-up retrospective cohort study considering women specifically studied for breast cancer. After reviewing the mammograms of 1759 women, we selected 128 patients with BAC and an equal number of women without BAC. Results: Women with BAC had higher relative risk (RR) for cardiovascular events, globally 1.66 (95% CI): 1.31–2.10 vs. 0.53 (0.39–0.72), and individually for ischemic heart disease 3.25 (1.53–6.90) vs. 0.85 (0.77–0.94), hypertensive heart disease 2.85 (1.59–5.09) vs. 0.79 (0.69–0.89), valvular heart disease 2.19 (1.28–3.75) vs. 0.83 (0.73–0.94), congestive heart failure 2.06 (1.19–3.56) vs. 0.85 (0.75–0.96), peripheral vascular disease 2.8 (1.42–5.52) vs. 0.85 (0.76–0.94), atrial fibrillation 1.83 (1.09–3.08) vs. 0.86 (0.76–0.98), and lacunar infarction 2.23 (1.21–4.09) vs. 0.86 (0.77–0.96). Cox’s multivariate analysis, also considering classical risk factors, indicated that this BAC was significantly and independently associated with survival (both cardiovascular event-free and specific survival; 1.94 (1.38–2.73) and 6.6 (2.4–18.4)). Conclusions: Our data confirm the strong association of BAC on mammograms and the development cardiovascular events, but also evidence the association of BAC with cardiovascular event-free and specific survival. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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11 pages, 1165 KiB  
Article
Incidence, Risk Factors and Clinical Implications of Glucose Metabolic Changes after Heart Transplant
by Emanuele Durante-Mangoni, Domenico Iossa, Valeria Iorio, Irene Mattucci, Umberto Malgeri, Daniela Pinto, Roberto Andini, Ciro Maiello and Rosa Zampino
Biomedicines 2022, 10(11), 2704; https://doi.org/10.3390/biomedicines10112704 - 26 Oct 2022
Viewed by 1420
Abstract
Diabetes mellitus (DM) arising de novo after transplant is a common complication, sharing many features with type 2 DM but also specific causes, such as administration of steroids and immunosuppressive drugs. Although post-transplant DM (PTDM) is generally assumed to worsen recipients’ outcomes, its [...] Read more.
Diabetes mellitus (DM) arising de novo after transplant is a common complication, sharing many features with type 2 DM but also specific causes, such as administration of steroids and immunosuppressive drugs. Although post-transplant DM (PTDM) is generally assumed to worsen recipients’ outcomes, its impact on renal function, cardiac allograft vasculopathy and mortality remains understudied in heart transplant (HT). We evaluated incidence and risk factors of PTDM and studied glucose metabolic alterations in relation to major HT outcomes. 119 subjects were included in this retrospective, single centre, observational study. A comprehensive assessment of glucose metabolic state was done pre-transplant and a median of 60 months [IQR 30–72] after transplant. Most patients were males (75.6%), with prior non-ischemic cardiomyopathy (64.7%) and median age of 58 years [IQR 48–63]. 14 patients developed PTDM, an incidence of 3.2 cases/100 patient-years. Patients with worsening glucose metabolic pattern were the only who showed a significant increase of BMI and metabolic syndrome prevalence after transplant. 23 (19.3%) patients died during follow up. Early mortality was lower in those with stably normal glucose metabolism, whereas improvement of glucose metabolic state favorably affected mid-term mortality (log-rank p = 0.028). No differences were observed regarding risk of infections and cancer. PTDM is common, but glucose metabolism may also improve after HT. PTDM is strictly related with BMI increase and metabolic syndrome development and may impact recipient survival. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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10 pages, 687 KiB  
Article
Associations of Warfarin Use with Risks of Ischemic Cerebrovascular Events and Major Bleeding in Patients with Hyperthyroidism-Related Atrial Fibrillation
by Sian-De Liu, Shwu-Jiuan Lin, Chin-Ying Ray, Fang-Tsyr Lin, Weei-Chin Lin and Li-Hsuan Wang
Biomedicines 2022, 10(11), 2670; https://doi.org/10.3390/biomedicines10112670 - 22 Oct 2022
Cited by 1 | Viewed by 1783
Abstract
The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 [...] Read more.
The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and 168 hyperthyroidism-related AF patients with mean (SD) age of 59.9 ± 13.5 and 59.2 ± 14.6 in the warfarin-treated group and untreated group separately. The mean (SD) CHA2DS2-VASc scores for the two groups were 2.1 ± 1.6 and 1.8 ± 1.5, respectively. Patients with hyperthyroidism-related AF receiving warfarin had no significant risk of ischemic stroke/TIA (adjusted HR: 1.16, 95% confidence interval [CI]: 0.52–2.56, p = 0.717) compared to nonusers. There was a comparable risk of major bleeding between those receiving warfarin or not (adjusted HR: 0.91, 95% CI: 0.56–1.47, p = 0.702). The active-comparator design also demonstrated that warfarin use had no significant association with the risk of stroke/TIA versus aspirin use (adjusted HR: 2.43; 95% CI: 0.68–8.70). In conclusion, anticoagulation therapy did not have a statistically significant benefit on ischemic stroke/TIA nor risk of bleeding, among patients with new-onset hyperthyroidism-related AF under a low CHA2DS2-VASc score, by comparing those without use. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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14 pages, 4846 KiB  
Article
Tetrahydrobiopterin (BH4) Supplementation Prevents the Cardiorenal Effects of Diabetes in Mice by Reducing Oxidative Stress, Inflammation and Fibrosis
by Ulises Novoa, Karen Soto, Cristian Valdés, Jorge Villaseñor, Adriana V. Treuer and Daniel R. González
Biomedicines 2022, 10(10), 2479; https://doi.org/10.3390/biomedicines10102479 - 4 Oct 2022
Cited by 3 | Viewed by 2137
Abstract
Background: The effects of diabetes on the cardiovascular system as well as in the kidney are profound, which include hypertrophy and fibrosis. Diabetes also induces oxidative stress, at least in part due to the uncoupling of nitric oxide synthase (NOS); this is a [...] Read more.
Background: The effects of diabetes on the cardiovascular system as well as in the kidney are profound, which include hypertrophy and fibrosis. Diabetes also induces oxidative stress, at least in part due to the uncoupling of nitric oxide synthase (NOS); this is a shift in NO production toward superoxide production due to reduced levels of the NOS cofactor tetrahydrobiopterin (BH4). With this in mind, we tested the hypothesis that BH4 supplementation may prevent the development of diabetic cardiomyopathy and nephropathy. Methods: Diabetes was induced in Balb/c mice with streptozotocin. Then, diabetic mice were divided into two groups: one group provided with BH4 (sapropterin) in drinking water (daily doses of 15 mg/kg/day, during eight weeks) and the other that received only water. A third group of normoglycemic mice that received only water were used as the control. Results: Cardiac levels of BH4 were increased in mice treated with BH4 (p = 0.0019). Diabetes induced cardiac hypertrophy, which was prevented in the group that received BH4 (p < 0.05). In addition, hypertrophy was evaluated as cardiomyocyte cross-sectional area. This was reduced in diabetic mice that received BH4 (p = 0.0012). Diabetes induced cardiac interstitial fibrosis that was reduced in mice that received BH4 treatment (p < 0.05). We also evaluated in the kidney the impact of BH4 treatment on glomerular morphology. Diabetes induced glomerular hypertrophy compared with normoglycemic mice and was prevented by BH4 treatment. In addition, diabetic mice presented glomerular fibrosis, which was prevented in mice that received BH4. Conclusions: These results suggest that chronic treatment with BH4 in mice ameliorates the cardiorenal effects of diabetes,, probably by restoring the nitroso–redox balance. This offers a possible new alternative to explore a BH4-based treatment for the organ damage caused by diabetes. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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9 pages, 1531 KiB  
Article
Association of N-Acetyl Asparagine with QTc in Diabetes: A Metabolomics Study
by Giacomo Gravina, Melissa Y. Y. Moey, Edi Prifti, Farid Ichou, Olivier Bourron, Elise Balse, Fabio Badillini, Christian Funck-Brentano and Joe-Elie Salem
Biomedicines 2022, 10(8), 1955; https://doi.org/10.3390/biomedicines10081955 - 12 Aug 2022
Cited by 1 | Viewed by 2616
Abstract
Changes in the cardio-metabolomics profile and hormonal status have been associated with long QT syndrome, sudden cardiac death and increased mortality. The mechanisms underlying QTc duration are not fully understood. Therefore, an identification of novel markers that complement the diagnosis in these patients [...] Read more.
Changes in the cardio-metabolomics profile and hormonal status have been associated with long QT syndrome, sudden cardiac death and increased mortality. The mechanisms underlying QTc duration are not fully understood. Therefore, an identification of novel markers that complement the diagnosis in these patients is needed. In the present study, we performed untargeted metabolomics on the sera of diabetic patients at a high risk of cardiovascular disease, followed up for 2.55 [2.34–2.88] years (NCT02431234), with the aim of identifying the metabolomic changes associated with QTc. We used independent weighted gene correlation network analysis (WGCNA) to explore the association between metabolites clusters and QTc at T1 (baseline) and T2 (follow up). The overlap of the highly correlated modules at T1 and T2 identified N-Acetyl asparagine as the only metabolite in common, which was involved with the urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine. This analysis was confirmed by applying mixed models, further highlighting its association with QTc. In the current study, we were able to identify a metabolite associated with QTc in diabetic patients at two chronological time points, suggesting a previously unrecognized potential role of N-Acetyl asparagine in diabetic patients suffering from long QTc. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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22 pages, 3964 KiB  
Article
Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients
by Zahra Abedi Kichi, Lucia Natarelli, Saeed Sadeghian, Mohammad ali Boroumand, Mehrdad Behmanesh and Christian Weber
Biomedicines 2022, 10(7), 1736; https://doi.org/10.3390/biomedicines10071736 - 19 Jul 2022
Cited by 3 | Viewed by 2705
Abstract
Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body’s ineffective use of insulin and is largely the result of excess body weight and physical inactivity. T2D increases the risk [...] Read more.
Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body’s ineffective use of insulin and is largely the result of excess body weight and physical inactivity. T2D increases the risk of cardiovascular diseases, retinopathy, and kidney failure by two-to three-fold. Hyperglycemia, as a hallmark of diabetes, acts as a potent stimulator of inflammatory condition by activating endothelial cells and by dysregulating monocyte activation. G-protein couple receptors (GPCRs) can both exacerbate and promote inflammatory resolution. Genome-wide association studies (GWAS) indicate that GPCRs are differentially regulated in inflammatory and vessel cells from diabetic patients. However, most of these GPCRs are orphan receptors, for which the mechanism of action in diabetes is unknown. Our data indicated that orphan GPCR26 is downregulated in the PBMC isolated from T2D patients. In contrast, GPR26 was initially upregulated in human monocytes and PBMC treated with high glucose (HG) levels and then decreased upon chronic and prolonged HG exposure. GPR26 levels were decreased in T2D patients treated with insulin compared to non-insulin treated patients. Moreover, GPR26 inversely correlated with the BMI and the HbA1c of diabetic compared to non-diabetic patients. Knockdown of GPR26 enhanced monocyte ROS production, MAPK signaling, pro-inflammatory activation, monocyte adhesion to ECs, and enhanced the activity of Caspase 3, a pro-apoptotic molecule. The same mechanisms were activated by HG and exacerbated when GPR26 was knocked down. Hence, our data indicated that GPR26 is initially activated to protect monocytes from HG and is inhibited under chronic hyperglycemic conditions. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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12 pages, 1622 KiB  
Article
Ldlr-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet
by Weibin Shi, Jing Li, Kelly Bao, Mei-Hua Chen and Zhenqi Liu
Biomedicines 2022, 10(6), 1429; https://doi.org/10.3390/biomedicines10061429 - 16 Jun 2022
Cited by 2 | Viewed by 2962
Abstract
Apoe-/- and Ldlr-/- mice are two animal models extensively used for atherosclerosis research. We previously reported that Apoe-/- mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related [...] Read more.
Apoe-/- and Ldlr-/- mice are two animal models extensively used for atherosclerosis research. We previously reported that Apoe-/- mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related traits in C3H-Ldlr-/- mice through comparing with C3H-Apoe-/- mice. On a chow diet, Ldlr-/- mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than Apoe-/- mice. Fasting plasma glucose was much lower in Ldlr-/- than Apoe-/- mice (male: 122.5 ± 5.9 vs. 229.4 ± 17.5 mg/dL; female: 144.1 ± 12.4 vs. 232.7 ± 6.4 mg/dL). When fed a Western diet, Ldlr-/- and Apoe-/- mice developed severe hypercholesterolemia and also hyperglycemia with fasting plasma glucose levels exceeding 250 mg/dL. Both knockouts had similar non-HDL cholesterol and triglyceride levels, and their fasting glucose levels were also similar. Male Ldlr-/- mice exhibited greater glucose tolerance and insulin sensitivity compared to their Apoe-/- counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though Ldlr-/- mice had higher non-fasting glucose levels. Male Ldlr-/- and Apoe-/- mice developed moderate obesity on the Western diet, but female mice did not. These results indicate that the Western diet and ensuing hyperlipidemia lead to the development of type 2 diabetes, irrespective of underlying genetic causes. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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Review

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20 pages, 800 KiB  
Review
Role of the Endocannabinoid System in Metabolic Control Processes and in the Pathogenesis of Metabolic Syndrome: An Update
by Gabriella Dörnyei, Zsolt Vass, Csilla Berta Juhász, György L. Nádasy, László Hunyady and Mária Szekeres
Biomedicines 2023, 11(2), 306; https://doi.org/10.3390/biomedicines11020306 - 21 Jan 2023
Cited by 14 | Viewed by 5626
Abstract
Metabolic syndrome is a complex disease state, which appears mostly as a consequence of an unhealthy, sedentary lifestyle. Metabolic complications include insulin resistance (IR), diabetes, dyslipidemia, hypertension, and atherosclerosis, impairing life standards and reducing life expectancy. The endocannabinoid system (ECS) has an important [...] Read more.
Metabolic syndrome is a complex disease state, which appears mostly as a consequence of an unhealthy, sedentary lifestyle. Metabolic complications include insulin resistance (IR), diabetes, dyslipidemia, hypertension, and atherosclerosis, impairing life standards and reducing life expectancy. The endocannabinoid system (ECS) has an important role in signalization processes, not only in the central nervous system, but also in the peripheral tissues. Several physiological functions are affected, and overexpression or downregulation contributes to several diseases. A better understanding of the functions of cannabinoid (CB) receptors may propose potential therapeutic effects by influencing receptor signaling and enzymes involved in downstream pathways. In this review, we summarize recent information regarding the roles of the ECS and the CB1 receptor signaling in the physiology and pathophysiology of energy and metabolic homeostasis, in the development of obesity by enhancing food intake, upregulating energy balance and fat accumulation, increasing lipogenesis and glucose production, and impairing insulin sensitivity and secretion. By analyzing the roles of the ECS in physiological and pathophysiological mechanisms, we introduce some recently identified signaling pathways in the mechanism of the pathogenesis of metabolic syndrome. Our review emphasizes that the presence of such recently identified ECS signaling steps raises new therapeutic potential in the treatment of complex metabolic diseases such as diabetes, insulin resistance, obesity, and hypertension. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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19 pages, 360 KiB  
Review
Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials
by Andreina Carbone, Roberta Bottino, Antonello D’Andrea and Vincenzo Russo
Biomedicines 2023, 11(1), 131; https://doi.org/10.3390/biomedicines11010131 - 4 Jan 2023
Cited by 7 | Viewed by 2860
Abstract
Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal efficacy in stroke prevention and greater safety in terms of intracranial bleeding. [...] Read more.
Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal efficacy in stroke prevention and greater safety in terms of intracranial bleeding. The study population in the randomized trials of DOACs was highly selected, so the results of these trials cannot be extended to specific populations such as obese, elderly, frail, and cancer patients, which, on the other hand, are sub-populations widely represented in clinical practice. Furthermore, due to the negative results of DOAC administration in patients with mechanical heart valves, the available evidence in subjects with biological heart valves is still few and often controversial. We sought to review the available literature on the efficacy and safety of DOACs in elderly, obese, underweight, frail, cancer patients, and in patients with bioprosthetic heart valves with NVAF to clarify the best anticoagulant strategy in these special and poorly studied subpopulations. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
13 pages, 1429 KiB  
Review
Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis
by Susumu Z. Sudo, Tadeu L. Montagnoli, Bruna de S. Rocha, Aimeé D. Santos, Mauro P. L. de Sá and Gisele Zapata-Sudo
Biomedicines 2022, 10(12), 3258; https://doi.org/10.3390/biomedicines10123258 - 15 Dec 2022
Cited by 15 | Viewed by 7899
Abstract
Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence [...] Read more.
Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence of diabetes is increasing, a concomitant increase in CAN is expected and will reduce quality of life and increase mortality. Autonomic dysfunction is associated with reduced baroreflex sensitivity and impairment of sympathetic and parasympathetic modulation. Various autonomic function tests are used to diagnose CAN, a condition without adequate treatment. It is important to consider the control of glucose level and blood pressure as key factors for preventing CAN progression. However, altered biomarkers of inflammatory and endothelial function, increased purinergic receptor expression, and exacerbated oxidative stress lead to possible targets for the treatment of CAN. The present review describes the molecular alterations seen in CAN, diagnosis, and possible alternative treatments. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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Review
Novel Therapies for the Treatment of Cardiac Fibrosis Following Myocardial Infarction
by Kamila Raziyeva, Yevgeniy Kim, Zharylkasyn Zharkinbekov, Kamila Temirkhanova and Arman Saparov
Biomedicines 2022, 10(9), 2178; https://doi.org/10.3390/biomedicines10092178 - 2 Sep 2022
Cited by 27 | Viewed by 5701
Abstract
Cardiac fibrosis is a common pathological consequence of most myocardial diseases. It is associated with the excessive accumulation of extracellular matrix proteins as well as fibroblast differentiation into myofibroblasts in the cardiac interstitium. This structural remodeling often results in myocardial dysfunctions such as [...] Read more.
Cardiac fibrosis is a common pathological consequence of most myocardial diseases. It is associated with the excessive accumulation of extracellular matrix proteins as well as fibroblast differentiation into myofibroblasts in the cardiac interstitium. This structural remodeling often results in myocardial dysfunctions such as arrhythmias and impaired systolic function in patients with heart conditions, ultimately leading to heart failure and death. An understanding of the precise mechanisms of cardiac fibrosis is still limited due to the numerous signaling pathways, cells, and mediators involved in the process. This review article will focus on the pathophysiological processes associated with the development of cardiac fibrosis. In addition, it will summarize the novel strategies for anti-fibrotic therapies such as epigenetic modifications, miRNAs, and CRISPR technologies as well as various medications in cellular and animal models. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions)
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