This review identifies multiple molecular mechanisms, including calcium handling defects, mitochondrial dysfunction, oxidative stress, neurohormonal activation, and fibrosis, that contribute to progressive left ventricular systolic dysfunction leading to heart failure.
Left ventricular systolic dysfunction results from complex structural, cellular, and molecular disorders affecting the contractile apparatus of the myocardium and its energy homeostasis. This review discusses the key mechanisms of this process, with emphasis on myocardial contraction and its regulation by calcium dynamics and integrity of the sarcomeres. The main factors leading to the development of systolic dysfunction are presented: volume and tension overload, ischemia, in ammation, amyloid and other deposits, neurohormonal activation and endocrine disorders, oxidative stress. In addition, cellular and molecular mechanisms are presented, such as defects in SERCA2a, and Na+/Ca 2+ exchanger, pathological Ca 2+ ef ux through RyR2, alterations in titin phosphorylation, myo lament damage, proteasome dysfunction, impaired autophagy, epigenetic regulation, endoplasmic reticulum stress, and abnormalities in intercellular connectivity. The complex interaction between these processes leads to progressive myocardial remodeling, brosis, energy de cit, and impaired myocardial contractility. Understanding these mechanisms is important for better understanding the pathogenesis of systolic dysfunction as well as for the development of new therapeutic strategies for its treatment.
Ivanov et al. (Wed,) conducted a review in Patients with left ventricular systolic dysfunction due to various etiologies including volume overload, pressure overload, ischemia, inflammation, oxidative stress, endocrine and metabolic disorders. This review identifies multiple molecular mechanisms, including calcium handling defects, mitochondrial dysfunction, oxidative stress, neurohormonal activation, and fibrosis, that contribute to progressive left ventricular systolic dysfunction leading to heart failure.