Am J Physiol Heart Circ Physiol
October 2024
Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the locus have been linked with sex-dependent obesity-associated traits; however, this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function, we subjected young and aged global SSPN-deficient (SSPN) male and female mice to obesogenic conditions (60% fat diet).
View Article and Find Full Text PDFThe protein sarcospan (SSPN) is an integral member of the dystrophin-glycoprotein complex (DGC) and has been shown to be important in the heart during the development and the response to acute stress. In this study, we investigated the role of SSPN in the cardiac response to acute ischemia-reperfusion (IR) injury in SSPN-deficient (SSPN) mice. First, the hemodynamic response of SSPN mice was tested and was similar to SSPN (wild-type) mice after isoproterenol injection.
View Article and Find Full Text PDFThe rising prevalence of obesity presents a world-wide challenge as it is associated with numerous comorbidities including cardiovascular disease, insulin resistance and hypertension. Obesity-associated illnesses are estimated to cause nearly 4 million deaths globally per year, therefore there is a critical need to better understand associated pathogenesis, identify new therapeutic targets, and develop new interventions. Emerging data identify a key role for chronic inflammation in mediating obesity related disease states and reveal higher incidence of autoimmune disease development.
View Article and Find Full Text PDFCardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC's αD-helix (-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-domain, favoring the "primed" state associated with Ca binding.
View Article and Find Full Text PDFPurpose Of Review: The world is currently facing the largest global health crisis since the early 1900s due to a novel . While SARS-CoV-2 infection causes predictable symptoms in COVID-19 patients, including upper respiratory distress and fever, the heterogeneity of manifestations is surprising. This review focuses on direct and indirect causes of myocardial injury in COVID-19 patients and highlights current knowledge, treatment strategies, and outstanding questions in the field.
View Article and Find Full Text PDFThe dystrophin-glycoprotein complex (DGC), situated at the sarcolemma dynamically remodels during cardiac disease. This review examines DGC remodeling as a common denominator in diseases affecting heart function and health. Dystrophin and the DGC serve as broad cytoskeletal integrators that are critical for maintaining stability of muscle membranes.
View Article and Find Full Text PDFHeart disease remains the number one killer of women in the US. Nonetheless, studies in women and female animal models continue to be underrepresented in cardiac research. Hypertrophic cardiomyopathy (HCM), the most commonly inherited cardiac disorder, has been tied to sarcomeric protein variants in both sexes.
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