New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

Abstract

Abstract. Cardiac hypertrophy is an increase in the muscle volume of the ventricle due to the enlargement of cardiac cells. Physiological cardiac hypertrophy is the normal response to healthy exercise, and pathological hypertrophy is the response to increased stress such as hypertension. Intracellular and extracellular aniosmotic conditions also change cell volume. Since persistent cell swelling or cell shrinkage during aniosmotic conditions results in cell death, the ability to regulate cell volume is important for the maintenance of cellular homeostasis. Cell swelling activates a regulatory volume decrease (RVD) response in which solute leakage pathways are stimulated and solute with water exits cells, reducing the cell volume towards the original value. In cardiac cells, one of the essential factors for cell-volume regulation is the volume-regulated anion channel (VRAC). However, the relationship between cardiac hypertrophy and cell-volume regulation is not clear. In this review, we introduce our recent findings showing that the impairment of VRAC current is exhibited in ventricular cells from mice with cardiac hypertrophy induced by transverse aortic constriction. Similar results were shown in caveolin-3-deficient mice, which develop cardiac hypertrophy without pressure overload. These results suggest that VRAC will be a new target for protection from the development of cardiac hypertrophy.

Neuronal nitric oxide synthase in hypertension – an update

“…The fundamental mechanisms those cause these changes involve altered ion channels and transporters in the plasmalemmal membrane of cardiac myocytes; abnormal calcium handling in cardiac myocytes; metabolic derangement; sarcomere disorganization and changes in the wide spectrum of intracellular signaling pathways [6, 11–17] . Concomitant to the progression of hypertension-induced adverse remodeling of myocardium, a number of endogenous defense mechanisms can be triggered, which are involved in delaying and preventing the pathological processes.…”

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

“…cardioprotection; caveolae; caveolin-3; cholesterol; contractility; ischemia-reperfusion; membrane microdomains; opioid receptors SARCOLEMMAL MICRODOMAINS are critical regulators of cellular function and signaling (34) and may be important in sex-, age-, and disease-dependent differences in cardiac and vascular function (3,10,11,14,24,49,62). Caveolae are lipid rich (i.e., cholesterol and glycosphingolipid) microdomains containing scaffolding proteins, caveolins, that present as distinct molecular platforms for the regulation of cytoprotective and other signaling (52).…”

Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

“…Moreover, in contrast to physiologic hypertrophy, pathological cardiac remodelling is characterized by an irreversible phenotype status [11, 33]. For a detailed view of the molecular mechanisms underlying cardiac hypertrophy see [3, 11, 34, 35]. Figure 1 presents the main alterations in heart and myocyte morphology due to pathological and physiological stimuli.…”