International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 132-143 http://medscipublisher.com/index.php/ijmms 134 2.3 Impact on cardiac function and structure Hypertensive heart disease significantly impacts both the structure and function of the heart. The most prominent structural change is left ventricular hypertrophy (LVH), where the myocardium thickens to manage increased workload from elevated blood pressure. While LVH initially serves as a compensatory mechanism, it eventually becomes maladaptive, leading to decreased cardiac efficiency and increased risk of heart failure. LVH results in increased myocardial stiffness and reduced compliance, impairing diastolic filling and leading to diastolic dysfunction. This dysfunction is characterized by elevated left ventricular end-diastolic pressure, which can cause symptoms of heart failure even with preserved ejection fraction. Over time, systolic function may also deteriorate, leading to reduced ejection fraction and overt heart failure. Fibrosis is another critical structural change, involving the excessive deposition of extracellular matrix proteins within the myocardium. This process disrupts the normal architecture of the heart muscle, leading to decreased contractility and increased risk of arrhythmias. Fibrotic tissue is less capable of conducting electrical impulses, predisposing individuals to atrial fibrillation and ventricular arrhythmias. Hypertension-induced endothelial dysfunction contributes to the structural remodeling of both the myocardium and vasculature. Endothelial dysfunction impairs the vasodilatory response, increases vascular resistance, and promotes atherosclerosis, further compromising coronary blood flow and myocardial oxygen supply. In summary, hypertensive heart disease leads to a complex interplay of structural and functional changes that progressively impair cardiac performance and increase the risk of adverse cardiovascular events. Early detection and management are crucial to mitigate these effects and improve patient outcomes (Bhargava et al., 2017). 3 Epigenetic Mechanisms in Hypertensive Heart Disease Epigenetic mechanisms, including DNA methylation, play a crucial role in the pathophysiology of hypertensive heart disease. DNA methylation involves the addition of a methyl group to the DNA molecule, typically at cytosine-phosphate-guanine (CpG) sites, which can alter gene expression without changing the DNA sequence itself. This modification has been extensively studied in the context of cardiovascular diseases, including hypertensive heart disease. 3.1 DNA methylation DNA methylation impacts genes related to cardiac function and structure, and its aberrant patterns have been linked to hypertensive heart disease. Genome-wide studies in hypertensive patients have identified differentially methylated regions (DMRs) associated with key genes involved in cardiac hypertrophy and myocardial dysfunction. For example, Liu et al. (2019) demonstrated that hypertensive rats exhibited significant changes in DNA methylation profiles, which were partially reversed by choline treatment, leading to improved cardiac function (Liu et al., 2019). Studies have shown that hypertensive patients exhibit lower global DNA methylation levels in peripheral blood mononuclear cells compared to normotensive individuals. This hypomethylation is associated with increased expression of genes that promote hypertension and cardiac hypertrophy. For example, DNA methylation changes in the promoter regions of the renin-angiotensin-aldosterone system (RAAS) genes, such as the angiotensin-converting enzyme (ACE) and angiotensinogen (AGT), have been linked to altered gene expression and elevated blood pressure (Friso et al., 2015). Furthermore, specific genes related to sodium homeostasis, such as the sodium-potassium-chloride cotransporter (NKCC1) and the epithelial sodium channel (ENaC), have shown differential methylation patterns in hypertensive individuals. These changes in methylation can lead to increased sodium reabsorption, contributing to hypertension and subsequent cardiac damage (Gonzalez-Jaramillo et al., 2019). Similarly, de la Rocha et al. (2020) discussed the potential of DNA hypermethylation as a biomarker for cardiovascular diseases, despite some inconsistencies in study findings (de la Rocha et al., 2020).
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