Cardioprotective proteins

Cardioprotective proteins represent a diverse functional class of endogenous and exogenous molecules that safeguard the myocardium against injury, particularly ischemia-reperfusion injury and toxic insults such as chemotherapy (1, 2). This category encompasses a wide range of molecular types, including molecular chaperones like heat shock protein 70 (HSP70), antioxidant enzymes such as heme oxygenase-1 (HO-1) and superoxide dismutase (SOD), and metabolic regulators like sestrins and sirtuins (3, 10). These proteins often serve as the downstream effectors of well-characterized signaling cascades, such as the Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways, which are triggered by the activation of specific G protein-coupled receptors like the adenosine or GLP-1 receptors (5, 12, 13). In the context of cardiovascular disease, therapeutic strategies aim to pharmacologically induce or supplement these proteins to limit infarct size, prevent adverse remodeling, and reduce the progression to heart failure (4, 9). While many individual proteins within this group are promising therapeutic targets, the term itself describes a collective biological outcome rather than a single druggable entity (1, 2).

Other names

Heart-protective proteinsEndogenous cardioprotectantsMyocardial protective proteinsCytoprotective proteins

Drugs targeting cardioprotective pathways typically act as agonists for G protein-coupled receptors (e.g., adenosine, GLP-1, or opioid receptors) or as inhibitors of cell death effectors (e.g., mPTP inhibitors), leading to the upregulation or activation of endogenous cardioprotective proteins that preserve mitochondrial function and cellular viability.