Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis

Abstract

Reperfusion after myocardial ischemia can induce cardiomyocyte death, known as myocardial reperfusion injury. The pathophysiology of the process of reperfusion suggests the confluence multiple pathways. Recent studies have focused on the inflammatory response, which is considered to be the main mechanism during the process of myocardial ischemia-reperfusion injury and can cause cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors gamma activated by endogenous ligands and exogenous ligand can decrease the inflammatory response in cardiomyocytes. Thiazolidinediones are synthetic, high-affinity, selective ligands for peroxisome proliferator-activated receptors gamma, and can inhibit the inflammatory response, decrease myocardial infarct size, and protect cardiac function. However, thiazolidinediones, including rosiglitazone and pioglitazone, can also contribute to adverse cardiovascular events such as congestive heart failure. Therefore, there are some limitations to the use of thiazolidinediones. Most endogenous ligands were of low affinity until hexadecyl azelaoyl phosphatidylcholine was identified as a high-affinity ligand and agonist for peroxisome proliferator-activated receptors gamma. Hexadecyl azelaoyl phosphatidylcholine binds recombinant peroxisome proliferator-activated receptors with an affinity (Kd(app) ≈40 nM) which is equivalent to rosiglitazone. Therefore, hexadecyl azelaoyl phosphatidylcholine is a specific peroxisome proliferator-activated receptors gamma agonist. Given these findings, we hypothesized that the use of hexadecyl azelaoyl phosphatidylcholine can activate the peroxisome proliferator-activated receptors gamma signal pathways and prevent the inflammatory response process of myocardial ischemia-reperfusion injury, with reduced cardiomyocyte apoptosis and death.

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway

“…The locally released riskrelated molecular pattern initiates and triggers the NODlike receptor protein 3 inflammasome, and enhances the inflammatory response and cell death through activating caspase-1 (23). Many studies have shown that inhibition of the inflammatory response can reduce cardiomyocyte apoptosis in the pathological process of myocardial I/R injury (24). Our study found that Art treatment suppressed myocardial apoptosis.…”

RETRACTED ARTICLE: LncRNA TUG1 protects against cardiomyocyte ischaemia reperfusion injury by inhibiting HMGB1

“…The incidence of coronary heart disease with acute myocardial infarction is increased worldwide now [2]. In the process of blood flow reperfusion, however, it leads to a large number of inflammatory cells aggregation in the myocardium of original ischaemia, serious damage to vascular endothelial function, obvious metabolic dysfunction, arrhythmia, myocardial apoptosis [3][4][5]. It is the main cause of serious cardiac complications even death after coronary revascularization and heart transplantation [6,7].…”

Understanding PPARγ and Its Agonists on Trophoblast Differentiation and Invasion: Potential Therapeutic Targets for Gestational Diabetes Mellitus and Preeclampsia

“…A summary of reported PPARγ ligands is provided in Table 1. GW1929 [16] Betulinic acid [17] SR-202 [18] Oxidized LDL [19] TZD *** NFκB [20] BADGE [21] EETs [22] FMOC-L-Leucine [23] Fetuin A [20] LG100641 [24] 15d-PGJ2 [25] INT131 [26] PD068235 [27] Azelaoyl phosphatidylcholine [28] Farglitazar (GI262570) [29] T0070907 [30] 9-oxoODE [31] S26948 [32] GW9662 [33] 13-oxoODE [34] AZ 242 [35] 15-HETE [36] LG100754 [37] 13-HODE [36] * Partial ligands of PPARγ such as telmisartan [38], Irbesartan [39], metaglidasen [40], and non-TZD partial agonist (nTZDpa) [41] are not included. ** poly-unsaturated FAs γ-linolenic (18:3), eicosatrienoic acid (C20:3), dihomoγ-linolenic (20:3), arachidonic acid (C20:4), and eicosapentaenoic acid (C20:5).…”