Heart failure with preserved ejection fraction: main molecular and cellular mechanisms of development
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https://orcid.org/0009-0006-5334-7333
Abstract
Heart failure with preserved ejection fraction (HFpEF) is characterized by signs and symptoms of heart failure in the presence of a normal left ventricular ejection fraction. HFpEF is a heterogeneous syndrome with diverse etiology and pathophysiological factors. HFpEF is a disease that develops by several pathophysiological mechanisms, although many of them remain unclear due to limited access to human heart tissue. At the heart of the mechanisms of HFpEF pathogenesis are disturbances in the handling of calcium ions in cardiomyocytes and endothelial dysfunction, which occurs as a result of numerous factors. Endothelial defects usually include impaired vasodilation, increased vasoconstriction, arterial stiffness, and atherogenesis. Endothelial dysfunction, the main consequence of which is insufficient NO availability, is associated with adverse events in patients with HFpEF. Compared with HFpEF patients without coronary endothelial dysfunction, patients with impaired endothelial function are characterized by more severe clinical outcomes, especially those associated with type 2 diabetes and obesity.
In the heart tissue of an adult, there are mixed populations of macrophages. The ratio of macrophages of different origins changes with aging and the progression of various CVDs, depending on gender and type of cardiovascular dysfunction. Macrophages play important roles in the development and progression of СН. The role of macrophages in the pathogenesis of hypertension, obesity, diabetes, renal dysfunction, which are risk factors leading to СН, is crucial.
Analysis of human endomyocardial biopsies has shown that HFpEF patients exhibit a gene expression profile distinct from HfrEF patients and normal controls.
The study of these and other mechanisms of the pathogenesis of HFpEF will reveal new promising therapeutic targets for the treatment of heart failure.
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