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Cardiovascular Disease: Molecular Advances on Pathophysiology and Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 14356

Special Issue Editor


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Guest Editor
1. Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, Rome, Italy
2. Cardiology Unit, Fabrizio Spaziani Hospital, Frosinone, Italy
Interests: acute heart failure; chronic heart failure; biomarkers; pharmacology; coronary microvascular dysfunction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

Cardiovascular (CV) disease represents one of the main causes of morbidity and mortality worldwide, evidencing the relevance of improving its management and relentlessly seeking better treatments.

Among CV diseases, heart failure (HF) is a complex syndrome characterized by progressive systemic involvement leading to multiorgan dysfunction. There are several pathophysiological pathways involved in HF and, some of them are now investigated as new pharmacological targets, such as guanylate cyclase and myosin pathways. Besides the pharmacological treatment, interesting results have been observed regarding implantable electrical therapeutical technology, such as cardiac resynchronization therapy and the more recent results of cardiac contractility modulation, promising weapons to reduce the worsening of HF and CV death. Lastly, biomarkers, such as Brain Natriuretic Peptide and High Sensitivity Cardiac Troponin, have gained more and more important in the diagnosis and in the follow-up of HF often guiding the decisional making and allowing the clinician to tailor the treatments to the patient's needs.

Ischemic heart disease is the principal cause of death worldwide and the pathophysiology of lipid plaque formation is the key to the recent field of research, such as the increasing interest in lipid-lowering drugs. Moreover, beyond the traditional ischemic heart disease pathophysiology based on atherosclerotic disease, there are other pivotal mechanisms involved, such as microvascular dysfunction which may act together or regardless of atherosclerosis.

To better highlight the recent advances in cardiovascular diseases, this Special Issue will focus on new findings about pathophysiological, pharmacological and diagnostic fields in cardiovascular diseases.

Specifically, original articles reporting completely new results or reviews of current literature on these aspects of the disease will be taken into account. The Special Issue wants to focus on both basic and translational research as well as clinical evidence in order to have a more complete comprehension of all the new aspects of cardiovascular disease.

Dr. Andrea D'Amato
Guest Editor

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Keywords

  • cardiovascular disease
  • heart failure
  • biomarkers
  • pathophysiology
  • ischemic heart disease
  • atherosclerosis
  • coronary microvascular dysfunction
  • pharmacology

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Published Papers (7 papers)

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Research

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16 pages, 7072 KiB  
Article
Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats
by Jaroslaw Szponar, Agnieszka Gorska, Marta Ostrowska-Lesko, Agnieszka Korga-Plewko, Michal Tchorz, Erwin Ciechanski, Anna Dabrowska, Ewa Poleszak, Franciszek Burdan, Jaroslaw Dudka, Marek Murias and Slawomir Mandziuk
Int. J. Mol. Sci. 2024, 25(4), 2219; https://doi.org/10.3390/ijms25042219 - 13 Feb 2024
Viewed by 1341
Abstract
Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. [...] Read more.
Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study’s findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels. Full article
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15 pages, 1691 KiB  
Article
Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients
by Vadim Genkel, Ilya Dolgushin, Albina Savochkina, Karina Nikushkina, Irina Baturina, Anna Minasova, Veronika Sumerkina, Lubov Pykhova, Semen Kupriyanov, Alla Kuznetsova and Igor Shaposhnik
Int. J. Mol. Sci. 2023, 24(15), 12205; https://doi.org/10.3390/ijms241512205 - 30 Jul 2023
Viewed by 1243
Abstract
Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study [...] Read more.
Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40–64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12–24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0–467.0 cells/μL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642–0.815) versus 0.637 (0.539–0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression. Full article
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Review

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24 pages, 3966 KiB  
Review
Sleep Apnea and Heart Failure—Current State-of-The-Art
by Tushar Menon and Dinesh K. Kalra
Int. J. Mol. Sci. 2024, 25(10), 5251; https://doi.org/10.3390/ijms25105251 - 11 May 2024
Cited by 4 | Viewed by 2700
Abstract
Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness [...] Read more.
Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB. Full article
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16 pages, 17556 KiB  
Review
Intrastent Restenosis: A Comprehensive Review
by Ioan-Teodor Bajeu, Adelina-Gabriela Niculescu, Alexandru Scafa-Udriște and Ecaterina Andronescu
Int. J. Mol. Sci. 2024, 25(3), 1715; https://doi.org/10.3390/ijms25031715 - 30 Jan 2024
Cited by 6 | Viewed by 3007
Abstract
The primary objective of this paper is to delineate and elucidate the contemporary advancements, developments, and prevailing trajectories concerning intrastent restenosis (ISR). We aim to provide a thorough overview of the most recent developments in this area, covering various aspects such as pathophysiological [...] Read more.
The primary objective of this paper is to delineate and elucidate the contemporary advancements, developments, and prevailing trajectories concerning intrastent restenosis (ISR). We aim to provide a thorough overview of the most recent developments in this area, covering various aspects such as pathophysiological insights, therapeutic approaches, and new strategies for tackling the complex challenges of ISR in modern clinical settings. The authors have undertaken a study to address a relatively new medical challenge, recognizing its significant impact on the morbidity and mortality of individuals with cardiovascular diseases. This effort is driven by the need to fully understand, analyze, and possibly improve the outcomes of this emerging medical issue within the cardiovascular disease field. We acknowledge its considerable clinical implications and the necessity for innovative methods to mitigate its effects on patient outcomes. Therefore, our emphasis was directed towards elucidating the principal facets of the condition’s prevalence, expounding upon the foundational mechanisms underscoring conspicuous restenosis, and delineating the risk factors relevant in shaping the contemporary landscape of diagnostic and therapeutic modalities. This thorough examination aims to provide a comprehensive understanding of the various dimensions of the condition, including epidemiological data, pathophysiological complexities, and clinical considerations critical for evaluating and enhancing current diagnostic and treatment approaches. Full article
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21 pages, 2240 KiB  
Review
Current Insights and Future Directions in the Treatment of Heart Failure with Preserved Ejection Fraction
by Roxana Mihaela Chiorescu, Roxana-Daiana Lazar, Alexandru Ruda, Andreea Paula Buda, Stefan Chiorescu, Mihaela Mocan and Dan Blendea
Int. J. Mol. Sci. 2024, 25(1), 440; https://doi.org/10.3390/ijms25010440 - 28 Dec 2023
Cited by 1 | Viewed by 1520
Abstract
Heart failure is a clinical syndrome associated with poor quality of life, substantial healthcare resource utilization, and premature mortality, in large part related to high rates of hospitalizations. The clinical manifestations of heart failure are similar regardless of the ejection fraction. Unlike heart [...] Read more.
Heart failure is a clinical syndrome associated with poor quality of life, substantial healthcare resource utilization, and premature mortality, in large part related to high rates of hospitalizations. The clinical manifestations of heart failure are similar regardless of the ejection fraction. Unlike heart failure with reduced ejection fraction, there are few therapeutic options for treating heart failure with preserved ejection fraction. Molecular therapies that have shown reduced mortality and morbidity in heart failure with reduced ejection have not been proven to be effective for patients with heart failure and preserved ejection fraction. The study of pathophysiological processes involved in the production of heart failure with preserved ejection fraction is the basis for identifying new therapeutic means. In this narrative review, we intend to synthesize the existing therapeutic means, but also those under research (metabolic and microRNA therapy) for the treatment of heart failure with preserved ejection fraction. Full article
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18 pages, 1111 KiB  
Review
Sizing SGLT2 Inhibitors Up: From a Molecular to a Morpho-Functional Point of View
by Silvia Prosperi, Andrea D’Amato, Paolo Severino, Vincenzo Myftari, Sara Monosilio, Ludovica Marchiori, Lucrezia Maria Zagordi, Domenico Filomena, Gianluca Di Pietro, Lucia Ilaria Birtolo, Roberto Badagliacca, Massimo Mancone, Viviana Maestrini and Carmine Dario Vizza
Int. J. Mol. Sci. 2023, 24(18), 13848; https://doi.org/10.3390/ijms241813848 - 8 Sep 2023
Cited by 3 | Viewed by 1856
Abstract
Sodium–glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known [...] Read more.
Sodium–glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known glucose reduction power. The cardioprotective effects of gliflozins seem to be linked to the maintenance of cellular homeostasis and to an action on the main metabolic pathways. They improve the oxygen supply for cardiomyocytes with a considerable impact on both functional and morphological myocardial aspects. Moreover, multiple molecular actions of SGLT2i are being discovered, such as the reduction of both inflammation, oxidative stress and cellular apoptosis, all responsible for myocardial damage. Various studies showed controversial results concerning the role of SGLT2i in reverse cardiac remodeling and the lowering of natriuretic peptides, suggesting that their overall effect has yet to be fully understood. In addition to this, advanced imaging studies evaluating the effect on all four cardiac chambers are lacking. Further studies will be needed to better understand the real impact of their administration, their use in daily practice and how they can contribute to benefits in terms of reverse cardiac remodeling. Full article
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13 pages, 1568 KiB  
Review
Immunomodulation Therapies for Atherosclerosis: The Past, the Present, and the Future
by Dalgisio Lecis, Gianluca Massaro, Daniela Benedetto, Marco Di Luozzo, Giulio Russo, Alessandro Mauriello, Massimo Federici and Giuseppe Massimo Sangiorgi
Int. J. Mol. Sci. 2023, 24(13), 10979; https://doi.org/10.3390/ijms241310979 - 1 Jul 2023
Cited by 2 | Viewed by 1919
Abstract
Atherosclerotic cardiovascular disease is the most common cause of morbidity and death worldwide. Recent studies have demonstrated that this chronic inflammatory disease of the arterial wall can be controlled through the modulation of immune system activity. Many patients with cardiovascular disease remain at [...] Read more.
Atherosclerotic cardiovascular disease is the most common cause of morbidity and death worldwide. Recent studies have demonstrated that this chronic inflammatory disease of the arterial wall can be controlled through the modulation of immune system activity. Many patients with cardiovascular disease remain at elevated risk of recurrent events despite receiving current, state-of-the-art preventive medical treatment. Much of this residual risk is attributed to inflammation. Therefore, finding new treatment strategies for this category of patients became of common interest. This review will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk, explicitly focusing on vaccination strategies. Full article
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