International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 132-143 http://medscipublisher.com/index.php/ijmms 133 This study investigates the role of epigenetic biomarkers in patients with hypertensive heart disease (HHD). By identifying specific epigenetic modifications associated with HHD, we aim to enhance early diagnosis, improve risk stratification, and discover potential new therapeutic targets. The study focuses on various epigenetic mechanisms, including DNA methylation patterns, histone modifications, and non-coding RNA profiles, to understand their contribution to the pathogenesis of HHD. Additionally, it examines the correlation between these epigenetic markers and clinical outcomes, as well as their potential as non-invasive biomarkers for HHD. The research also provides insights into the molecular pathways altered in HHD and how regulating these changes can offer therapeutic benefits. By advancing the understanding of the epigenetic landscape in HHD, we hope to pave the way for precision medicine approaches that tailor treatments based on an individual's epigenetic profile, ultimately improving patient care and prognosis. 2 Pathophysiology of Hypertensive Heart Disease 2.1 Mechanisms of hypertension-induced cardiac damage Hypertensive heart disease (HHD) results from the chronic increase in blood pressure that exerts excessive pressure on the cardiovascular system, leading to a cascade of pathological changes. The primary mechanism involves left ventricular hypertrophy (LVH), where the heart muscle thickens to counteract the increased workload. This hypertrophic response initially helps maintain cardiac output but eventually leads to maladaptive changes. One key mechanism is myocardial fibrosis, characterized by the excessive deposition of extracellular matrix proteins, primarily collagen, in the heart tissue. Fibrosis reduces myocardial compliance and contributes to diastolic dysfunction. Elevated blood pressure also causes endothelial dysfunction, which impairs the ability of blood vessels to dilate properly. This dysfunction is partly due to reduced nitric oxide availability and increased oxidative stress, which further promotes inflammation and fibrosis (Eirin et al., 2014). Neurohormonal activation, particularly of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, plays a significant role. These systems elevate blood pressure and induce hypertrophic and fibrotic responses in the myocardium. Chronic RAAS activation leads to the overproduction of angiotensin II, which stimulates fibroblast proliferation and collagen synthesis. Sympathetic activation increases heart rate and contractility, exacerbating myocardial stress. Microvascular remodeling occurs, characterized by increased vascular resistance and reduced coronary blood flow. This remodeling contributes to ischemia and further cardiac damage. Together, these mechanisms lead to a cycle of progressive cardiac dysfunction and increased risk of heart failure and other cardiovascular events (Nwabuo and Vasan, 2020). 2.2 Genetic vs. epigenetic influences on HHD The development of hypertensive heart disease is influenced by both genetic and epigenetic factors. Genetic predispositions, such as polymorphisms in genes related to blood pressure regulation, myocardial structure, and fibrosis, contribute to the risk of HHD. However, these genetic factors alone do not fully explain the variability in disease manifestation and progression. Epigenetic modifications, which involve changes in gene expression without altering the DNA sequence, are critical in modulating the impact of genetic predispositions and environmental factors. DNA methylation, histone modifications, and non-coding RNAs are primary epigenetic mechanisms influencing HHD. For instance, DNA methylation patterns can alter the expression of genes involved in myocardial hypertrophy and fibrosis. Histone modifications can change chromatin structure, affecting gene transcription relevant to cardiac function and response to hypertension. Non-coding RNAs, such as microRNAs, also play significant roles in HHD. These small RNA molecules can post-transcriptionally regulate gene expression by targeting messenger RNAs for degradation or translational repression. Specific microRNAs have been identified that modulate pathways involved in cardiac hypertrophy, fibrosis, and inflammation. Epigenetic changes can be influenced by environmental factors, such as diet, physical activity, and stress, making them potential targets for therapeutic intervention. Understanding the interplay between genetic and epigenetic factors is crucial for developing personalized treatment strategies for HHD (Soler-Botija et al., 2019).
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