Research

10 pages, 1118 KiB

Open AccessArticle

DNA Methylation of the IL-17A Gene Promoter Is Associated with Subclinical Atherosclerosis and Coronary Artery Disease: The Genetics of Atherosclerotic Disease Mexican Study

by Nonanzit Pérez-Hernández, Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Óscar Pérez-Méndez, María Luna-Luna and José Manuel Rodríguez-Pérez

Curr. Issues Mol. Biol. 2023, 45(12), 9768-9777; https://doi.org/10.3390/cimb45120610 - 05 Dec 2023

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Abstract

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter [...] Read more.

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38–14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06–0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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12 pages, 2665 KiB

Open AccessCommunication

Antioxidant Flavonoid Diosmetin Is Cardioprotective in a Rat Model of Myocardial Infarction Induced by Beta 1-Adrenergic Receptors Activation

by Taseer Ahmad, Taous Khan, Annet Kirabo and Abdul Jabbar Shah

Curr. Issues Mol. Biol. 2023, 45(6), 4675-4686; https://doi.org/10.3390/cimb45060297 - 29 May 2023

Cited by 1 | Viewed by 1899

Abstract

Myocardial infarction (MI) is a common and life-threatening manifestation of ischemic heart diseases (IHD). The most important risk factor for MI is hypertension. Natural products from medicinal plants have gained considerable attention globally due to their preventive and therapeutic effects. Flavonoids have been [...] Read more.

Myocardial infarction (MI) is a common and life-threatening manifestation of ischemic heart diseases (IHD). The most important risk factor for MI is hypertension. Natural products from medicinal plants have gained considerable attention globally due to their preventive and therapeutic effects. Flavonoids have been found to be efficacious in ischemic heart diseases (IHD) by alleviating oxidative stress and beta-1 adrenergic activation, but the mechanistic link is not clear. We hypothesized that antioxidant flavonoid diosmetin is cardioprotective in a rat model of MI induced by beta 1-adrenergic receptor activation. To test this hypothesis, we evaluated the cardioprotective potential of diosmetin on isoproterenol-induced MI in rats by performing lead II electrocardiography (ECG), cardiac biomarkers including troponin I (cTnI) and creatinine phosphokinase (CPK), CK-myocardial band, (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotranferase (AST) by using biolyzer 100, as well as histopathological analysis. We found that diosmetin (1 and 3 mg/kg) attenuated isoproterenol-induced elevation in the T-wave and deep Q-wave on the ECG, as well as heart-to-body weight ratio and infarction size. In addition, pretreatment with diosmetin attenuated the isoproterenol-induced increase in serum troponin I. These results demonstrate that flavonoid diosmetin may provide therapeutic benefit in myocardial infarction. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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15 pages, 3600 KiB

Open AccessArticle

Apolipoprotein E (APOE) Haplotypes in Healthy Subjects from Worldwide Macroareas: A Population Genetics Perspective for Cardiovascular Disease, Neurodegeneration, and Dementia

by Paolo Abondio, Francesco Bruno and Donata Luiselli

Curr. Issues Mol. Biol. 2023, 45(4), 2817-2831; https://doi.org/10.3390/cimb45040184 - 31 Mar 2023

Cited by 3 | Viewed by 1711

Abstract

Human APOE is a 299-amino acid long protein expressed and secreted in several tissues and body districts, where it exerts different functions mainly related to lipid metabolism, with specific activities around cholesterol transport and absorption/elimination. It has three main isoforms, determined by the [...] Read more.

Human APOE is a 299-amino acid long protein expressed and secreted in several tissues and body districts, where it exerts different functions mainly related to lipid metabolism, with specific activities around cholesterol transport and absorption/elimination. It has three main isoforms, determined by the pair of mutations rs7412-C/T and rs429358-C/T, which gives rise to the functionally different APOE variants ε2, ε3, and ε4. These have a distinct impact on lipid metabolism and are differentially implicated in Alzheimer’s disease and neurodegeneration, cardiovascular disease, and dyslipidemia. A plethora of other single nucleotide variants along the sequence of the APOE gene have been studied in cohorts of affected individuals, where they also modulate the influence of the three main isoforms to determine the risk of developing the disease. However, no contextual analysis of gene-long haplotypes has been carried out so far, and never extensively in cohorts of healthy individuals from different worldwide populations. Leveraging a rich population genomics dataset, this study elucidates the distribution of APOE variants and haplotypes that are shared across populations and to specific macroareas, revealing a variety of risk-allele associations that distinguish specific ancestral backgrounds and can be leveraged for specific ancestry-informed screenings in medicine and public health. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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Review

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28 pages, 2442 KiB

Open AccessReview

To Repair a Broken Heart: Stem Cells in Ischemic Heart Disease

by Theodora M. Stougiannou, Konstantinos C. Christodoulou, Ioannis Dimarakis, Dimitrios Mikroulis and Dimos Karangelis

Curr. Issues Mol. Biol. 2024, 46(3), 2181-2208; https://doi.org/10.3390/cimb46030141 - 08 Mar 2024

Viewed by 1071

Abstract

Despite improvements in contemporary medical and surgical therapies, cardiovascular disease (CVD) remains a significant cause of worldwide morbidity and mortality; more specifically, ischemic heart disease (IHD) may affect individuals as young as 20 years old. Typically managed with guideline-directed medical therapy, interventional or [...] Read more.

Despite improvements in contemporary medical and surgical therapies, cardiovascular disease (CVD) remains a significant cause of worldwide morbidity and mortality; more specifically, ischemic heart disease (IHD) may affect individuals as young as 20 years old. Typically managed with guideline-directed medical therapy, interventional or surgical methods, the incurred cardiomyocyte loss is not always completely reversible; however, recent research into various stem cell (SC) populations has highlighted their potential for the treatment and perhaps regeneration of injured cardiac tissue, either directly through cellular replacement or indirectly through local paracrine effects. Different stem cell (SC) types have been employed in studies of infarcted myocardium, both in animal models of myocardial infarction (MI) as well as in clinical studies of MI patients, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), Muse cells, multipotent stem cells such as bone marrow-derived cells, mesenchymal stem cells (MSCs) and cardiac stem and progenitor cells (CSC/CPCs). These have been delivered as is, in the form of cell therapies, or have been used to generate tissue-engineered (TE) constructs with variable results. In this text, we sought to perform a narrative review of experimental and clinical studies employing various stem cells (SC) for the treatment of infarcted myocardium within the last two decades, with an emphasis on therapies administered through thoracic incision or through percutaneous coronary interventions (PCI), to elucidate possible mechanisms of action and therapeutic effects of such cell therapies when employed in a surgical or interventional manner. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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17 pages, 14565 KiB

Open AccessReview

COVID-19 Associated Cardiovascular Disease—Risks, Prevention and Management: Heart at Risk Due to COVID-19

by Andrew Kemerley, Abhishek Gupta, Mahesh Thirunavukkarasu, Monica Maloney, Sean Burgwardt and Nilanjana Maulik

Curr. Issues Mol. Biol. 2024, 46(3), 1904-1920; https://doi.org/10.3390/cimb46030124 - 29 Feb 2024

Viewed by 1026

Abstract

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus and the resulting COVID-19 pandemic have had devastating and lasting impact on the global population. Although the main target of the disease is the respiratory tract, clinical outcomes, and research have also shown significant effects [...] Read more.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus and the resulting COVID-19 pandemic have had devastating and lasting impact on the global population. Although the main target of the disease is the respiratory tract, clinical outcomes, and research have also shown significant effects of infection on other organ systems. Of interest in this review is the effect of the virus on the cardiovascular system. Complications, including hyperinflammatory syndrome, myocarditis, and cardiac failure, have been documented in the context of COVID-19 infection. These complications ultimately contribute to worse patient outcomes, especially in patients with pre-existing conditions such as hypertension, diabetes, or cardiovascular disease (CVD). Importantly and interestingly, reports have demonstrated that COVID-19 also causes myocardial injury in adults without pre-existing conditions and contributes to systemic complications in pediatric populations, such as the development of multisystem inflammatory syndrome in children (MIS-C). Although there is still a debate over the exact mechanisms by which such complications arise, understanding the potential paths by which the virus can influence the cardiovascular system to create an inflammatory environment may clarify how SARS-CoV-2 interacts with human physiology. In addition to describing the mechanisms of disease propagation and patient presentation, this review discusses the diagnostic findings and treatment strategies and the evolution of management for patients presenting with cardiovascular complications, focusing on disease treatment and prevention. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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22 pages, 954 KiB

Open AccessReview

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine

by Younan Samuel, Aswin Babu, Foteini Karagkouni, Ayden Ismail, Sunyoung Choi and Stergios Boussios

Curr. Issues Mol. Biol. 2023, 45(10), 8337-8358; https://doi.org/10.3390/cimb45100526 - 15 Oct 2023

Viewed by 1863

Abstract

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors [...] Read more.

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient’s cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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22 pages, 1481 KiB

Open AccessReview

The Link between Magnesium Supplements and Statin Medication in Dyslipidemic Patients

by Roxana Nartea, Brindusa Ilinca Mitoiu and Ioana Ghiorghiu

Curr. Issues Mol. Biol. 2023, 45(4), 3146-3167; https://doi.org/10.3390/cimb45040205 - 05 Apr 2023

Cited by 4 | Viewed by 5702

Abstract

Many investigations have discovered a connection between statins and magnesium supplements. On one hand, increasing research suggests that chronic hypomagnesemia may be an important factor in the etiology of some metabolic illnesses, including obesity and overweight, insulin resistance and type 2 diabetes mellitus, [...] Read more.

Many investigations have discovered a connection between statins and magnesium supplements. On one hand, increasing research suggests that chronic hypomagnesemia may be an important factor in the etiology of some metabolic illnesses, including obesity and overweight, insulin resistance and type 2 diabetes mellitus, hypertension, alterations in lipid metabolism, and low-grade inflammation. Chronic metabolic problems seem to be prevented by a high Mg intake combined with diet and/or supplements. On the other hand, it is known that statins lower the frequency of cardiac events, stroke, and mortality, not by lowering LDL-C, but by the capacity to reduce mevalonate formation. That will enhance endothelial function, inhibit vascular smooth muscle cell proliferation and migration and encourage macrophages to promote plaque stability and regression while reducing inflammation. Taking these factors into consideration, we did an extensive analysis of the relevant literature, comparing the effects of Mg² and statin medications on lipoproteins and, implicitly, on the key enzymes involved in cholesterol metabolism. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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Other

Jump to: Research, Review

9 pages, 1236 KiB

Open AccessCase Report

A Novel Nonsense Pathogenic TTN Variant Identified in a Patient with Severe Dilated Cardiomyopathy

by Caterina Micolonghi, Marco Fabiani, Erika Pagannone, Camilla Savio, Marta Ricci, Silvia Caroselli, Vittoria Gambioli, Beatrice Musumeci, Aldo Germani, Giacomo Tini, Camillo Autore, Antonio Pizzuti, Vincenzo Visco, Speranza Rubattu, Simona Petrucci and Maria Piane

Curr. Issues Mol. Biol. 2023, 45(3), 2422-2430; https://doi.org/10.3390/cimb45030157 - 15 Mar 2023

Viewed by 1399

Abstract

Both genetic and environmental factors contribute to the development of dilated cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain 25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman diagnosed with severe DCM and presenting relevant [...] Read more.

Both genetic and environmental factors contribute to the development of dilated cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain 25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman diagnosed with severe DCM and presenting relevant acquired risk factors for DCM (hypertension, diabetes, smoking habit, and/or previous alcohol and cocaine abuse) and with a family history of both DCM and sudden cardiac death. The left ventricular systolic function, as assessed by standard echocardiography, was 20%. The genetic analysis performed using TruSight Cardio panel, including 174 genes related to cardiac genetic diseases, revealed a novel nonsense TTN variant (TTN:c.103591A > T, p.Lys34531*), falling within the M-band region of the titin protein. This region is known for its important role in maintaining the structure of the sarcomere and in promoting sarcomerogenesis. The identified variant was classified as likely pathogenic based on ACMG criteria. The current results support the need of genetic analysis in the presence of a family history, even when relevant acquired risk factors for DCM may have contributed to the severity of the disease. Full article

(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)

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