Abstract
Calcium homeostasis plays an essential role in maintaining excitation–contraction coupling (ECC) in cardiomyocytes, including calcium release, recapture, and storage. Disruption of calcium homeostasis may affect heart function, leading to the development of various heart diseases. Myocardial ischemia/reperfusion (MI/R) injury may occur after revascularization, which is a treatment used in coronary heart disease. MI/R injury is a complex pathological process, and the main cause of increased mortality and disability after treatment of coronary heart disease. However, current methods and drugs for treating MI/R injury are very scarce, not ideal, and have limitations. Studies have shown that MI/R injury can cause calcium overload that can further aggravate MI/R injury. Therefore, we reviewed the effects of critical calcium pathway regulators on MI/R injury and drew an intuitive diagram of the calcium homeostasis pathway. We also summarized and analyzed calcium pathway-related or MI/R drugs under research or marketing by searching Therapeutic Target and PubMed Databases. The data analysis showed that six drugs and corresponding targets are used to treat MI/R injury and involved in calcium signaling pathways. We emphasize the relevance of further detailed investigation of MI/R injury and calcium homeostasis and the therapeutic role of calcium homeostasis in MI/R injury, which bridges basic research and clinical applications of MI/R injury.
Highlights
Myocardial ischemia/reperfusion (MI/R) is an inevitable process in the treatment of cardiovascular diseases such as acute myocardial infarction, thrombolysis, coronary angioplasty, and cardiac arrest (Zhu et al, 2017)
Calcium levels in myocardial cells are regulated by L-type Ca2+ channels (LTCC), NCX, sarco (endo) plasmic reticulum Ca2+-ATPase (SERCA), ryanodine receptor 2 (RyR2), and mitochondria, which participate in calcium overload during MI/R injury (Landstrom et al, 2017)
Normal heart function depends on coordinated Ca2+ movement into and out of the plasma membrane and sarcoplasmic reticulum; calcium circulation disorders can cause various heart diseases
Summary
Myocardial ischemia/reperfusion (MI/R) is an inevitable process in the treatment of cardiovascular diseases such as acute myocardial infarction, thrombolysis, coronary angioplasty, and cardiac arrest (Zhu et al, 2017). Calcium levels in myocardial cells are regulated by LTCC, NCX, SERCA, RyR2, and mitochondria, which participate in calcium overload during MI/R injury (Landstrom et al, 2017). CaMKII can act on Ca2+-releasing proteins such as RyR2, LTCC, IP3R, and regulate calcium recalculation by PLB and SERCA phosphorylation (Maier and Bers, 2002). A study of an animal model of structural heart disease proved that CaMKII overexpression can lead to myocardial dilatation, dysfunction, and calcium homeostasis imbalance in cardiomyocytes (Grueter et al, 2006). When blood flow and oxygen supply to the cardiac tissue returns to normal, extracellular pH level is further increased, HNX and NCX activities are enhanced, and intracellular calcium overload is further aggravated (Murphy and Steenbergen, 2008). OFR can TABLE 1 | Summary of MI/R injury drugs
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