International Journal of Molecular Sciences

Editorial

Jump to: Research, Review

3 pages, 181 KiB

Open AccessEditorial

Novel Molecules in Diabetes Mellitus, Dyslipidemia and Cardiovascular Disease 2.0

by Cosmin Mihai Vesa and Simona Gabriela Bungău

Int. J. Mol. Sci. 2024, 25(17), 9527; https://doi.org/10.3390/ijms25179527 - 2 Sep 2024

Viewed by 675

Abstract

Diabetes mellitus, dyslipidemia and cardiovascular disorders represent very prevalent chronic diseases in developed countries contributing to a high morbidity and loss of quality of life [...] Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

Research

Jump to: Editorial, Review

20 pages, 2880 KiB

Open AccessArticle

Overexpression of miR-199b-5p in Colony Forming Unit-Hill’s Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression

by Sherin Bakhashab, Rosie Barber, Josie O’Neill, Catherine Arden and Jolanta U. Weaver

Int. J. Mol. Sci. 2024, 25(15), 8087; https://doi.org/10.3390/ijms25158087 - 25 Jul 2024

Viewed by 867

Abstract

Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated [...] Read more.

Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated following metformin therapy. Inflammatory and vascular markers were measured in 29 individuals with T1DM and 20 matched healthy controls (HCs). miR-199b-5p expression in CFU-Hill’s colonies was analyzed from each study group, and correlations with inflammatory/vascular health indices were evaluated. Significant upregulation of miR-199b-5p was observed in T1DM, which was significantly downregulated by metformin. miR-199b-5p correlated positively with vascular endothelial growth factor-D and c-reactive protein (CRP: nonsignificant). ROC analysis determined miR-199b-5p to define subclinical CVD by discriminating between HCs and T1DM individuals. ROC analyses of HbA1c and CRP showed that the upregulation of miR-199b-5p in T1DM individuals defined subclinical CVD at HbA1c > 44.25 mmol and CRP > 4.35 × 10⁶ pg/mL. Ingenuity pathway analysis predicted miR-199b-5p to inhibit the target genes SIRT1, ETS1, and JAG1. Metformin was predicted to downregulate miR-199b-5p via NFATC2 and STAT3 and reverse its downstream effects. This study validated the antiangiogenic properties of miR-199b-5p and substantiated miR-199b-5p overexpression as a biomarker of subclinical CVD. The downregulation of miR-199b-5p by metformin confirmed its cardio-protective effect. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Figure 1

12 pages, 515 KiB

Open AccessArticle

Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population

by Dominik Franciszek Dłuski, Marek Cieśla and Dorota Darmochwał-Kolarz

Int. J. Mol. Sci. 2024, 25(13), 7040; https://doi.org/10.3390/ijms25137040 - 27 Jun 2024

Viewed by 847

Abstract

Gestational diabetes mellitus (GDM) is an intolerance of carbohydrate of any degree, which appears for the first time or is diagnosed during pregnancy. The objective of this study is to assess the differences in circular RNA (circRNA) in a Polish pregnant population with [...] Read more.

Gestational diabetes mellitus (GDM) is an intolerance of carbohydrate of any degree, which appears for the first time or is diagnosed during pregnancy. The objective of this study is to assess the differences in circular RNA (circRNA) in a Polish pregnant population with and without GDM. A total of 62 pregnant women, 34 with GDM and 28 controls, were enrolled in the study. Total RNAs were extracted from plasma and reverse transcription to complementary DNA (cDNA) was performed. A panel covering 271 amplicons, targeting both linear and circular as well as negative control gene transcripts, was used. Next-generation sequencing was used to evaluate the circRNA quantity. Data analysis was performed using the Coverage Analysis plugin in the Torrent Suite Software (Torrent Suite 5.12.3). A two-step normalization was performed by dividing each transcript read count by the total number of reads generated for the sample, followed by dividing the quantity of each transcript by β-actin gene expression. Both circular and linear forms of RNAs were independently evaluated. A total of 57 transcripts were dysregulated between pregnant women with GDM and controls. Most of the targets (n = 25) were downregulated (cut-off ratio below 0.5), and one target showed a trend toward strong upregulation (ratio 1.45). A total of 39 targets were positively correlated with fasting plasma glucose (FPG), but none of the tested targets were correlated with insulin, CRP or HOMA-IR levels. Among the pregnant women with gestational diabetes, the relative quantity of hsa_circ_0002268 (PHACTR1) was approximately 120% higher than among healthy pregnant women: 0.046 [0.022–0.096] vs. 0.021 [0.007–0.047], respectively, (p = 0.0029). Elevated levels of hsa_circ_0002268 (PHACTR1) might be specific to the Polish population of pregnant women with GDM, making it useful as a potential molecular biomarker in the management of GDM in Poland. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Figure 1

13 pages, 2050 KiB

Open AccessArticle

Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human

by Alexandra Höpfinger, Andreas Schmid, Thomas Karrasch, Sabine Pankuweit, Andreas Schäffler and Karsten Grote

Int. J. Mol. Sci. 2024, 25(5), 2909; https://doi.org/10.3390/ijms25052909 - 2 Mar 2024

Cited by 2 | Viewed by 1239

Abstract

Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate [...] Read more.

Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate immune system and metabolism in these settings. We investigated systemic CAMP/CRAMP levels in experimental murine models of atherosclerosis, myocardial infarction and cardiovascular patients. Atherosclerosis was induced in low-density lipoprotein receptor-deficient (Ldlr^−/−) mice by high-fat diet (HFD). C57BL/6J wild-type mice were subjected to myocardial infarction by permanent or transient left anterior descending (LAD)-ligation. Cramp gene expression in murine organs and tissues was investigated via real-time PCR. Blood samples of 234 adult individuals with or without coronary artery disease (CAD) were collected. Human and murine CAMP/CRAMP serum levels were quantified by ELISA. Atherosclerotic mice exhibited significantly increased CRAMP serum levels and induced Cramp gene expression in the spleen and liver, whereas experimental myocardial infarction substantially decreased CRAMP serum levels. Human CAMP serum quantities were not significantly affected by CAD while being correlated with leukocytes and pro-inflammatory cytokines. Our data show an influence of cathelicidin in experimental atherosclerosis, myocardial infarction, as well as in patients with CAD. Further studies are needed to elucidate the pathophysiological mechanism. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

18 pages, 1635 KiB

Open AccessReview

Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes

by Stéphane Dalle

Int. J. Mol. Sci. 2024, 25(12), 6425; https://doi.org/10.3390/ijms25126425 - 11 Jun 2024

Viewed by 1100

Abstract

The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass characterizes type 2 diabetes. To date, none of the available antidiabetic drugs promotes the maintenance of a functional mass of [...] Read more.

The prevalence of diabetes is increasing worldwide. Massive death of pancreatic beta-cells causes type 1 diabetes. Progressive loss of beta-cell function and mass characterizes type 2 diabetes. To date, none of the available antidiabetic drugs promotes the maintenance of a functional mass of endogenous beta-cells, revealing an unmet medical need. Dysfunction and apoptotic death of beta-cells occur, in particular, through the activation of intracellular protein kinases. In recent years, protein kinases have become highly studied targets of the pharmaceutical industry for drug development. A number of drugs that inhibit protein kinases have been approved for the treatment of cancers. The question of whether safe drugs that inhibit protein kinase activity can be developed and used to protect the function and survival of beta-cells in diabetes is still unresolved. This review presents arguments suggesting that several protein kinases in beta-cells may represent targets of interest for the development of drugs to treat diabetes. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Figure 1

28 pages, 1160 KiB

Open AccessReview

New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions

by Kyriazoula Chatzianagnostou, Melania Gaggini, Adrian Suman Florentin, Ludovica Simonini and Cristina Vassalle

Int. J. Mol. Sci. 2024, 25(11), 6218; https://doi.org/10.3390/ijms25116218 - 5 Jun 2024

Cited by 2 | Viewed by 1642

Abstract

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic [...] Read more.

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Graphical abstract

22 pages, 1630 KiB

Open AccessReview

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

by Teodora Bianca Sirca, Mariana Eugenia Mureșan, Annamaria Pallag, Eleonora Marian, Tunde Jurca, Laura Grațiela Vicaș, Ioana Paula Tunduc, Felicia Manole and Liana Ștefan

Int. J. Mol. Sci. 2024, 25(5), 2962; https://doi.org/10.3390/ijms25052962 - 4 Mar 2024

Cited by 3 | Viewed by 1748

Abstract

The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory [...] Read more.

The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), and high serum levels lead to a protective state against dyslipidemia, cardiovascular diseases, diabetes, stroke, nonalcoholic fatty liver disease, and many others. Modulating PON1 expression might be a treatment objective with significant results in limiting the prevalence of atherosclerosis. Lifestyle including diet and exercise can raise its levels, and some beneficial plants have been found to influence PON1 levels; therefore, more studies on herbal components are needed. Our purpose is to highlight the principal roles of Praoxonase 1, its implications in dyslipidemia, cardiovascular diseases, stroke, and other diseases, and to emphasize plants that can modulate PON1 expression, targeting the potential of some flavonoids that could be introduced as supplements in our diet and to validate the hypothesis that flavonoids have any effects regarding PON1 function. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Figure 1

25 pages, 1824 KiB

Open AccessReview

Cardiometabolic Risk: Characteristics of the Intestinal Microbiome and the Role of Polyphenols

by Ioana Mariana Haș, Delia Mirela Tit, Simona Gabriela Bungau, Flavia Maria Pavel, Bernadette-Emoke Teleky, Dan Cristian Vodnar and Cosmin Mihai Vesa

Int. J. Mol. Sci. 2023, 24(18), 13757; https://doi.org/10.3390/ijms241813757 - 6 Sep 2023

Cited by 4 | Viewed by 1798

Abstract

Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols [...] Read more.

Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols are primarily known for their anti-inflammatory and antioxidant properties, but they can also modify the gut microbiota. According to recent research, polyphenols positively influence the gut microbiota, which regulates metabolic responses and reduces systemic inflammation. This review emphasizes the prebiotic role of polyphenols and their impact on specific gut microbiota components in patients at cardiometabolic risk. It also analyzes the most recent research on the positive effects of polyphenols on cardiometabolic health. While numerous in vitro and in vivo studies have shown the interaction involving polyphenols and gut microbiota, additional clinical investigations are required to assess this effect in people. Full article

(This article belongs to the Special Issue Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Novel Molecules in Diabetes Melitus, Dyslipidemia and Cardiovascular Disease 2.0

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI