Recent advances on the role of monoamine oxidases in cardiac pathophysiology
AbstractNumerous physiological and pathological roles have been attributed to the formation of mitochondrial reactive oxygen species (ROS). However, the individual contribution of different mitochondrial processes independently of bioenergetics remains elusive and clinical treatments unavailable. A notable exception to this complexity is found in the case of monoamine oxidases (MAOs). Unlike other ROS-producing enzymes, especially within mitochondria, MAOs possess a distinct combination of defined molecular structure, substrate specificity, and clinically accessible inhibitors. Another significant aspect of MAO activity is...
Source: Basic Research in Cardiology - October 4, 2023 Category: Cardiology Source Type: research
Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation
AbstractActivation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD. Through structure-based virtual screening, pharmacological screening and subsequent pharmacological validations, we preliminarily identified GSDMD inhibitor Y1 (GI-Y1) as a selective GSDMD inhibitor with cardioprotective ...
Source: Basic Research in Cardiology - October 2, 2023 Category: Cardiology Source Type: research
Giant mitochondria in cardiomyocytes: cellular architecture in health and disease
AbstractGiant mitochondria are frequently observed in different disease models within the brain, kidney, and liver. In cardiac muscle, these enlarged organelles are present across diverse physiological and pathophysiological conditions including in ageing and exercise, and clinically in alcohol-induced heart disease and various cardiomyopathies. This mitochondrial aberration is widely considered an early structural hallmark of disease leading to adverse organ function. In this thematic paper, we discuss the current state-of-knowledge on the presence, structure and functional implications of giant mitochondria in heart musc...
Source: Basic Research in Cardiology - September 29, 2023 Category: Cardiology Source Type: research
The roles of intracellular proteolysis in cardiac ischemia –reperfusion injury
AbstractIschemic heart disease remains a leading cause of human mortality worldwide. One form of ischemic heart disease is ischemia –reperfusion injury caused by the reintroduction of blood supply to ischemic cardiac muscle. The short and long-term damage that occurs due to ischemia–reperfusion injury is partly due to the proteolysis of diverse protein substrates inside and outside of cardiomyocytes. Ischemia–reperfusion a ctivates several diverse intracellular proteases, including, but not limited to, matrix metalloproteinases, calpains, cathepsins, and caspases. This review will focus on the biological roles, intra...
Source: Basic Research in Cardiology - September 28, 2023 Category: Cardiology Source Type: research
Ketone body 3-hydroxybutyrate elevates cardiac output through peripheral vasorelaxation and enhanced cardiac contractility
AbstractThe ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output and myocardial perfusion without affecting blood pressure in humans, but the cardiovascular sites of action remain obscure. Here, we test the hypothesis in rats that 3-OHB acts directly on the heart to increase cardiac contractility and directly on blood vessels to lower systemic vascular resistance. We investigate effects of 3-OHB on (a) in vivo hemodynamics using echocardiography and invasive blood pressure measurements, (b) isolated perfused hearts in Langendorff systems, and (c) isolated arteries and veins in isometric myographs. We compare Na-3...
Source: Basic Research in Cardiology - September 9, 2023 Category: Cardiology Source Type: research
Myeloperoxidase is a critical mediator of anthracycline-induced cardiomyopathy
AbstractCardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells e...
Source: Basic Research in Cardiology - September 1, 2023 Category: Cardiology Source Type: research
Cardiac fibroblast GSK-3 α aggravates ischemic cardiac injury by promoting fibrosis, inflammation, and impairing angiogenesis
AbstractMyocardial infarction (MI) is the leading cause of death worldwide. Glycogen synthase kinase-3 (GSK-3) has been considered to be a promising therapeutic target for cardiovascular diseases. GSK-3 is a family of ubiquitously expressed serine/threonine kinases. GSK-3 isoforms appear to play overlapping, unique, and even opposing functions in the heart. Previously, our group identified that cardiac fibroblast (FB) GSK-3 β acts as a negative regulator of fibrotic remodeling in the ischemic heart. However, the role of FB-GSK-3α in MI pathology is not defined. To determine the role of FB-GSK-3α in MI-induced adverse ca...
Source: Basic Research in Cardiology - September 1, 2023 Category: Cardiology Source Type: research
Myeloperoxidase is a critical mediator of anthracycline-induced cardiomyopathy
AbstractCardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells e...
Source: Basic Research in Cardiology - September 1, 2023 Category: Cardiology Source Type: research
Cardiac fibroblast GSK-3 α aggravates ischemic cardiac injury by promoting fibrosis, inflammation, and impairing angiogenesis
AbstractMyocardial infarction (MI) is the leading cause of death worldwide. Glycogen synthase kinase-3 (GSK-3) has been considered to be a promising therapeutic target for cardiovascular diseases. GSK-3 is a family of ubiquitously expressed serine/threonine kinases. GSK-3 isoforms appear to play overlapping, unique, and even opposing functions in the heart. Previously, our group identified that cardiac fibroblast (FB) GSK-3 β acts as a negative regulator of fibrotic remodeling in the ischemic heart. However, the role of FB-GSK-3α in MI pathology is not defined. To determine the role of FB-GSK-3α in MI-induced adverse ca...
Source: Basic Research in Cardiology - September 1, 2023 Category: Cardiology Source Type: research
