Clinical and Molecular Implications of Osteopontin in Heart Failure

Abstract

The matricellular protein osteopontin modulates cell–matrix interactions during tissue injury and healing. A complex multidomain structure of osteopontin enables it not only to bind diverse cell receptors but also to interact with various partners, including other extracellular matrix proteins, cytokines, and growth factors. Numerous studies have implicated osteopontin in the development and progression of myocardial remodeling in diverse cardiac diseases. Osteopontin influences myocardial remodeling by regulating extracellular matrix production, the activity of matrix metalloproteinases and various growth factors, inflammatory cell recruitment, myofibroblast differentiation, cardiomyocyte apoptosis, and myocardial vascularization. The exploitation of osteopontin loss- and gain-of-function approaches in rodent models provided an opportunity for assessment of the cell- and disease-specific contribution of osteopontin to myocardial remodeling. In this review, we summarize the recent knowledge on osteopontin regulation and its impact on various cardiac diseases, as well as delineate complex disease- and cell-specific roles of osteopontin in cardiac pathologies. We also discuss the current progress of therapeutics targeting osteopontin that may facilitate the development of a novel strategy for heart failure treatment.

Recent Advances of Proteomics in Management of Acute Kidney Injury

“…Annexin A1, also known as lipocortin, has been mainly controlled by glucocorticoids hormons and cytosolic phospholipase A2 (PLA2) inhibition, responsible for the mechanism of arachidonic acid (ARA) release and the prevention of signaling molecules (eicosanoids) synthesis [ 137 , 138 , 139 ]. The protein itself has binding affinity to the phospholipid layers of the cell membranes, hence making it a molecular target for monitoring treatment response through cross-linkage with formyl peptide receptors [ 140 ]. With similar properties, cytoplasmatic annexin A2 has been largerly studied for its roles in intracellular regulation and cell signaling cascades [ 141 ].…”

The Role of Biochemical Cardiac Markers in Atrial Fibrillation

“…A few of the cell types in the heart that produce OPN in response to various stimuli, such as hypoxia, inflammation, toxin exposure, and mechanical stretching, include cardiomyocytes, cardiac fibroblasts, resident macrophages, and coronary artery endothelial cells. 74 OPN is an extracellular matrix protein that plays an integral role in myocardial remodeling and has previously been shown to be a valuable biomarker in CVD. 75 OPN, a plasma-detectable glycoprotein found to be elevated in various animal models of cardiac failure, may therefore constitute a new biomarker that makes it simpler for patients with HF to categorize their risks.…”

Cardioprotective Effects of Hydrogen Sulfide and Its Potential Therapeutic Implications in the Amelioration of Duchenne Muscular Dystrophy Cardiomyopathy

“…In contrast, we have demonstrated that NaHS treatment leads to a reduction in the OPN level in the plasma and muscles (gastrocnemius, tibialis anterior, and diaphragm) of mdx mice [162]. The role of OPN in the progression of cardiovascular diseases and heart failure is undeniable, and it was demonstrated in studies utilizing OPNnull mice and experiments with its depletion by neutralizing antibodies or via targeted mutagenesis (reviewed in [163,164]). It may also significantly influence DMD-related cardiomyopathy [165].…”