Abstract
The objective of this work is to inquire whether the myocardial ischemia (MI) could lead to plasma lipid metabolism disorders and Danqi Pill (DQP)’s pharmacological effects on coronary heart disease (CHD). Ameroid ring was placed on left anterior descending coronary artery (LAD) to prepare CHD model of chronic MI on Chinese mini-swine. Echocardiography was employed to measure cardiac function. Enzyme-linked immunosorbent assay (ELISA) and Western blot was used to detect key molecules such as nitric oxide (NO), angiotensin II (Ang II), aldosterone (Ald), oxidized-low density lipoprotein (ox-LDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL)and NADPH oxidase (NOX4). Radioimmunoassay (RIA) was applied to evaluate the level of reactive oxygen species (ROS). Lipid metabolism disorder was mediated by MI, represented by the up-regulation of ox-LDL, LDL and VLDL, caused by RAAS activation. Plasma Ang II and Ald in model group were increased while NO decreased by 25.20%. NOX4 and ROS were also up-regulated significantly. Compared with model group, plasma Ang II and Ald in DQP group were decreased, while ox-LDL and LDL decreased, respectively and NO decreased by 47.60%. NOX4 and malondialdehyde (MDA) almost returned to normal level. Echocardiograph showed that ejection fraction (EF) improved significantly, with the improvement of left ventricular end-diastolic diameter (LVEDd). MI can lead to plasma lipid metabolism disorders and RAAS activation. DQP can down-regulate plasma Ang II and Ald, thus to reduce the ox-LDL and LDL level mediated by NOX4-ROS pathway; it also can increase NO levels, eventually promote heart function. Key words: Danqi pill, myocardial ischemia, lipid disorder, renin-angiotensin-aldosterone system (RAAS).
Highlights
Coronary heart disease (CHD) remains the major cause of death for adults worldwide (He et al, 2005)
Eight (8) weeks after surgery, echocardiography showed that, compared with the sham-operated animals, model group exhibited the expansion of left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVEDs) dimensions and volume
The western blot of NOX4 showed that at the end of the study, the NOX4 in model group increased by 62% (P < 0.05) compared with sham, while when treated with Danqi Pill (DQP) for 4 weeks, the level of NOX4 showed 35.80% reduction compared with model group (P < 0.05), which had no statistical significance compared to sham (Figure 3)
Summary
Coronary heart disease (CHD) remains the major cause of death for adults worldwide (He et al, 2005). Lipid metabolism disorder is an independent risk factor for CHD (Jaswal et al, 2011); lipid peroxidation induced by lipid infiltration is considered to be the main pathological mechanism of myocardial ischemia (MI) caused by coronary stenosis and atherosclerosis Even some critical proteins in lipid metabolism are used as new drug targets to treat or reduce the risk of CHD (Frayn et al, 2005). Whether the MI can induce the plasma lipid metabolism disorder in turn is poorly studied. Renin-angiotensin-aldosterone system (RAAS) activation is one of the most important cause contributing to ventricular hypertrophy and cardiac remodeling (Madamanchi et al, 2005), some researchers showed that they can induce vascular endothelial dysfunction to mediate lipid metabolism disorders (Papaharalambus and Griendling, 2007), these changes indicate that RAAS play
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