Mitochondrial dysfunction has been implicated in the pathogenesis of ischemic heart disease, exacerbating cardiomyocytes injury in myocardial infarction (MI). Peroxisome proliferator-activated receptor gamma co-activator (PGC-1α) has been recognized as the key regulator of mitochondrial biogenesis and energy metabolism. Yiqihuoxue decoction (YQHX), a Traditional Chinese Medicine (TCM) prescription, can prevent and treat ischemic heart disease. However, the mechanisms of YQHX on PGC-1α expression in the ischemic heart have remained unclear. Myocardial ischemia rat model and ischemia/hypoxia injury model in the cardiomyocytes were used to minic human cardiovascular disease. Rats were randomly assigned into 4 groups: Sham, Model, YQHX (8.2 g/kg) and Trimetazidine (10 mg/kg) group. 28 days after MI, cardiac functions and morphology were detected by echocardiography and HE staining, respectively. In vitro, the effects of YQHX on H9c2 cell viability, LDH and ROS were detected, respectively. PGC-1α relevant proteins were evaluated by Western blotting. In vivo, echocardiography and HE staining results showed that YQHX improved cardiac functions and modified pathological changes. YQHX enhanced PGC-1α expression and improved the mitochondrial ultrastructure and functions in rats MI model for 4 weeks. Further, we explored its potential mechanisms in cardiomyocytes. In vitro, YQHX significantly enhanced cell viability and reduced LDH release and ROS production induced by hypoxia in cardiomyocytes. Interestingly, exposure of cardiomyocytes to hypoxic conditions for 12 h induced the downregulation of PGC-1α expression, but the expression levels nearly returned to the normal state after hypoxia for 24 h. YQHX significantly enhanced PGC-1α expression between 12 h and 24 h induced by hypoxia through a mechanism associated with the activation of AMPK phosphorylation in H9c2 cells. In addition, YQHX upregulated the expression of Tfam and NRF-1, while NRF-1 expression was completely blocked by an AMPK inhibitor. YQHX largely restored the mitochondrial morphology and increased mitochondrial membrane potential in hypoxia-induced injury. Furthermore, the UHPLC-LTQ-Orbitrap-MSn analysis found that there were 87 chemical constituents in YQHX. These results suggest that the protective effect of YQHX on cardiomyocytes against hypoxia-induced injury may be attributed to activation of PGC-1α and maintenance of mitochondrial functions through a mechanism involving the activation of AMPK phosphorylation.

Ischemic heart disease (IHD), a major global public health problem, is associated with high morbidity and mortality. Although the very best of modern approaches have proven effective in reducing morbidity and mortality, the poor prognosis of patients with IHD remains a major clinical concern. Cardiac energy metabolism is increasingly recognized as having a role in the pathogenesis of IHD, inducing metabolic substrate alterations, mitochondrial dysfunction, impaired function of the mitochondrial electron transport chain, and deprivation of cardiac energy. Factors involved in cardiac energy metabolism provide potential therapeutic targets for the treatment of IHD. Chinese herbal medicines (CHMs) have a long history of use in the prevention and treatment of cardiovascular diseases with multi-component, multi-target, and multi-signaling. Increasing evidence suggests that Chinese herbal medicines may improve myocardial ischemia through modulating cardiac energy metabolism. Here, we describe the possible targets and pathways of cardiac energy metabolism for CHMs, and appraise the modulatory effects of CHMs on energy metabolism in IHD. Especially, this review focuses on summarizing the metabolic effects and the underlying mechanisms of Chinese herbal medicines (including herbs, major bioactive components, and formulas) in IHD. In addition, we also discuss the current limitations and the major challenges for research investigating the use of CHMs in the treatment of cardiovascular diseases.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide that bears an enormous healthcare burden and aging is a major contributing factor to CVDs. Functional gene expression network during aging is regulated by mRNAs transcriptionally and by non-coding RNAs epi-transcriptionally. RNA modifications alter the stability and function of both mRNAs and non-coding RNAs and are involved in differentiation, development, and diseases. Here we review major chemical RNA modifications on mRNAs and non-coding RNAs, including N6-adenosine methylation, N1-adenosine methylation, 5-methylcytidine, pseudouridylation, 2′ -O-ribose-methylation, and N7-methylguanosine, in the aging process with an emphasis on cardiovascular aging. We also summarize the currently available methods to detect RNA modifications and the bioinformatic tools to study RNA modifications. More importantly, we discussed the specific implication of the RNA modifications on mRNAs and non-coding RNAs in the pathogenesis of aging-associated CVDs, including atherosclerosis, hypertension, coronary heart diseases, congestive heart failure, atrial fibrillation, peripheral artery disease, venous insufficiency, and stroke.

Myocardial infarction can lead to ventricular remodeling and arrhythmia, which is closely related to nerve remodeling. Our previous study found that Yiqi Huoxue decoction (YQHX) can improve ventricular remodeling and reduce myocardial damage. Therefore, in this study, we observed the effect of YQHX on cardiac neural remodeling and cardiomyocyte hypertrophy and its possible mechanism. This research is composed of two parts: animal and H9c2 cells experiments. The animal model of acute myocardial infarction was established by ligating the left anterior descending coronary artery in Sprague Dawley (SD) rats. H9c2 cells were placed in 94 N₂, 5 CO₂, and 1 O₂ hypoxic environment for 12 hours to replicate the hypoglycemic hypoxia model. The experimental results showed that, compared with the MI group, YQHX can significantly improve heart function after myocardial infarction and reduce nerve remodeling and myocardial hypertrophy. Pathological structure observation demonstrated reducing myocardial tissue damage and decreasing of cell cross-sectional area, diameter, and circumference. The positive rate of TH declined apparently, and the sympathetic nerve density was lower than that of the MI group. After YQHX was given for 28 days, the proneural remodeling factors TH, NGF, and GAP43 in the marginal zone of infarction and stellate ganglion decreased obviously while the inhibitory nerve remodeling factor Sema-3A increased. The myocardial hypertrophic protein ANP and β-MHC were also significantly inhibited with p-ERK1/2 protein expression level prominently reduced. There was no difference between the YQHX group and the Meto group. After myocardial infarction, nerve remodeling was seen in the marginal area of infarction and stellate ganglion, and the neuropeptides released by which promoted myocardial hypertrophy. The mechanism may be related to the ERK1/2 signaling pathway. YQHX could regulate the ERK1/2 signaling pathway, inhibit the release of nerve remodeling factors and myocardial hypertrophy protein to reduce nerve remodeling, and relieve myocardial hypertrophy.