Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway

Abstract

Many studies reported that air pollution particulate matter (PM) exposure was associated with myocardial infarction (MI). Acrolein representing the unsaturated aldehydes, the main component of PM, derives from the incomplete combustion of wood, plastic, fossil fuels and the main constitute of cigarette smoking. However, the effect of acrolein on MI remains not that clear. In the current study, the effect of acrolein-exacerbated MI was investigated. In vivo, male Sprague–Dawley rats received olive leaf extract (OLE) followed by acrolein, then isoprenaline (ISO) was received by subcutaneous injection to induce MI. Results showed that the expression levels of GRP78 and CHOP, two major components of endoplasmic reticulum (ER) stress were higher in the combination of acrolein and ISO than those in ISO treatment. The apoptosis marker, Bax, was also higher while the anti-apoptosis indicator, Bcl2 expression was lower both at protein and mRNA levels in the combination group. Also, the acrolein-protein adducts and myocardial pathological damage increased in the combination of acrolein and ISO relative to the ISO treatment. Besides, cardiac parameters, ejection fraction (EF) and fractional shortening (FS) were reduced more significantly when acrolein was added than in ISO treatment. Interestingly, all the changes were able to be ameliorated by OLE. Since hydroxytyrosol (HT) and oleuropein (OP) were the main components in OLE, we next investigated the effect of HT and OP on cardiomyocyte H9c2 cell apoptosis induced by acrolein through ER stress and Bax pathway. Results showed that GRP78, CHOP and Bax expression were upregulated, while Bcl2 expression was downregulated both at the protein and mRNA levels, when the H9c2 cells were treated with acrolein. In addition, pretreatment with HT can reverse the expression of GRP78, CHOP, Bax and Bcl2 on the protein and mRNA levels, while there was no effect of OP on the expression of GRP78 and CHOP on the mRNA levels. Overall, all these results demonstrated that OLE and the main components (HT and OP) could prevent the negative effects of acrolein on myocardium and cardiomyocytes.

Cardioprotective effect of hemin in isoprenaline‐induced myocardial infarction: role of ATP‐sensitive potassium channel and endothelial nitric oxide synthase

“…Apoptosis markedly shares in mediation of MI including cleaved caspase‐3, TNFα, and BAX/Bcl‐2 pathway. We found the same in ISO‐ induced MI group, and this is in line with Xu et al , Kumar et al , Jana et al , and Bin‐Jaliah et al .…”

“…This imbalance with the excessive release of reactive oxygen species (ROS) is a major contributing factor in the development of MI. Free radicals attack membrane lipids and mediate a chain of reactions of lipid peroxidation associated with disruption of the structure and permeability of cell membranes .…”

“…The B‐cell lymphoma‐2 (Bcl‐2) family is a potent regulator of the apoptotic pathways. This family of proteins includes both anti‐apoptotic and pro‐apoptotic proteins such as Bcl‐2 associated X protein (Bax) and Bcl‐2, respectively . Moreover, oxidative stress has a key role in mediating MI and antioxidants represent the first line of defense against it.…”

Olive Leaf (<b><i>Olea europaea L. folium</i></b>): Potential Effects on Glycemia and Lipidemia

“…There are studies in the literature proving that olive leaf extract decreases endoplasmic reticulum stress, and thus it may also decrease myocardial infarction [51,52]. A study demonstrated that hydroxytyrosol and oleuropein decreased apoptosis and endoplasmic reticulum stress, induced by acrolein, in cardiomyocyte cells by reducing 78-kDa glucose-regulated protein, the C/EBP homologous protein, and Bax expression levels in rats [52].…”

“…There are studies in the literature proving that olive leaf extract decreases endoplasmic reticulum stress, and thus it may also decrease myocardial infarction [51,52]. A study demonstrated that hydroxytyrosol and oleuropein decreased apoptosis and endoplasmic reticulum stress, induced by acrolein, in cardiomyocyte cells by reducing 78-kDa glucose-regulated protein, the C/EBP homologous protein, and Bax expression levels in rats [52]. Another study supported the claim that hydroxytyrosol and olive leaf extract reversed the increase in C/EBP homologous protein and 78-kDa glucose-regulated protein expression levels induced by isoproterenol, and it may show cardioprotective effect by means of endoplasmic reticulum stress [51].…”