Osteopontin Promotes Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway

• Published in: Journal of the American College of Cardiology Vol. 73; no. 21; pp. 2705 - 2718
• Main Authors: Yousefi, Keyvan, Irion, Camila I., Takeuchi, Lauro M., Ding, Wen, Lambert, Guerline, Eisenberg, Trevor, Sukkar, Sarah, Granzier, Henk L., Methawasin, Mei, Lee, Dong I., Hahn, Virginia S., Kass, David A., Hatzistergos, Konstantinos E., Hare, Joshua M., Webster, Keith A., Shehadeh, Lina A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.06.2019; Elsevier Limited
• Subjects: Alport syndrome; Animals; Autoantigens - genetics; Bioenergetics; Cardiology; Cardiomyocytes; Cardiomyopathy; Cardiovascular; Collagen Type IV - genetics; Congestive heart failure; Coronary artery disease; Cytokines; Disease Models, Animal; Edema; Fibrosis; Flow velocity; Genetic Therapy; Genotype & phenotype; Heart failure; Heart Failure, Diastolic - etiology; Heart Failure, Diastolic - metabolism; Heart Failure, Diastolic - pathology; Heart Failure, Diastolic - therapy; HFpEF; Hip; hiPS-CM; Hypertension; Hypertrophy; Intermediates; Ketoglutarate Dehydrogenase Complex - genetics; Ketoglutarate Dehydrogenase Complex - metabolism; Ketoglutaric acid; Kidney diseases; Lung diseases; Mice; Mice, Knockout; Mitochondria; Mitochondria - metabolism; mRNA; Myocardium - metabolism; Myocardium - pathology; Nephritis, Hereditary - complications; OGDHL; Osteopontin; Osteopontin - genetics; Osteopontin - metabolism; Oxidative Stress; Oxoglutarate dehydrogenase (lipoamide); Patients; Phenotypes; Pluripotency; Pulmonary arteries; Renal failure; Renal function; Stem cells; Therapeutic applications; Ventricle; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - metabolism; hiPS-CM; hiPSC; osteopontin; mitochondria; Alport syndrome; OGDHL; CM; HFpEF; OPN; HFrEF; IVRT; isovolumetric relaxation time; cardiac myocyte; heart failure with preserved ejection fraction; 2-oxoglutarate dehydrogenase-like; heart failure with reduced ejection fraction; human-induced pluripotent stem cell

Patients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitoc...