[Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis].

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

[Research on Dynamic Evolution of Blockade of Heart Vessel Syndrome Based on Metabonomics].

Objective To observe the changes of metabolomics in the evolution process of blockade of heart vessel syndrome (BHVS). Methods The formation of BHVS in three stages were sim- ulated by using high-fat forage and ligating the left anterior descending coronary artery. Increased blood lipid was in the early stage of blood stasis syndrome (BSS) group. Atherosclerosis (AS) was formed in the middle stage of BSS group (sub-BSS). Coronary artery was ligated on the basis of AS was the 3rd stage of BSS (BHVS group). There were 8 rats in each group. Totally 24 rats was used as the blank con- trol group and each stage had 8 rats. The changes of metabolite contents were analyzed using principal component analysis (PCA) and partial least squares method (PLS) with gas chromatography-mass spectrometer (GC-MS) among different groups. Results (1) In the 32 kinds of identified metabolites, citric acid was closest associated with the evolution process of BHVS, followed by cholesterol, inositol, ornithine, proline, isoleucine, octadecanoic acid, lactic acid, urea, leucine, linoleic acid, mannose. (2) Metabolic markers in the three stages: octadecanoic acid, lactic acid (positively correlated) , and mannose (negatively correlated) in the early stage of BSS. Ornithine, proline, inositol (positively correla- ted) , and isoleucine (negatively correlated) in the middle stage of BSS (sub-BSS). Leucine, isoleucine, citric acid (positively correlated) , and lactic acid (negatively correlated) in the BHVS stage. Conclusions High fat diet causes disordered in vivo lipid metabolism in pre-stage BSS, and the organism initiates anti- inflammation. Continued high fat diet leads to disordered urea cycle, imbalanced intestinal flora, changed vascular morphology, and liver dysfunction in the sub-BSS stage. Acute myocardial ischemia leads to glucose metabolism disorder in the BHVS stage.

[Relevant Research on ACE Gene Single Nucleotide Polymorphisms and Premature Coronary Heart Disease Patients with Blood Stasis Syndrome].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene single nucleotide polymorphisms (SNP) and premature coronary heart disease (PCHD) patients with blood stasis syndrome (BSS). METHODS: rs4343, rs4293, and rs4267385 were selected at SNP from ACE gene. Allele and genotype were detected. Frequencies of allele and genotype were compared by using time-of-flight mass spectrometry technique (TOF-MS). RESULTS: Compared with the healthy control group, genotype of rs4293 and rs4267385 in ACE gene were similar, but there was statistical difference in polymorphisms and allele frequencies of rs4343 in the I and II group (P < 0.05, P < 0.01). The frequency of G allele was higher in the 3 groups than in the healthy control group (P < 0.05, P < 0.01). The relative risk analysis showed that the risk for PCHD occurrence in G allele carriers at rs4343 (GG +AG) was 3. 6 times the risk in non-G allele carriers (95% CI: 1.224-10.585, P = 0.02). There was also statistical difference in sex, age, TC, and TG after adjusted Logistic regression analysis (OR = 3.994, 95% CI: 1.230-12.974, P = 0.021). CONCLUSION: The polymorphism at rs4343 (G2350A) might be one of risk factors for PCHD occurrence, but not a predisposing factor for PCHD patients of BSS.

[Metabolomics study of the myocardial tissue of rats of cardiac blood stasis syndrome].

OBJECTIVE: To find out the metabolite profile of rats' myocardial tissue of cardiac blood stasis syndrome (CBSS), and to analyze the metabolic pathway of CBSS rats' myocardial tissue by observing the changes of phenotypes intervened by Yangxin Tongmai Recipe (YTR). METHODS: Acute myocardial infarction (AMI) rat model of CBSS was prepared by ligating the left anterior descending coronary artery. Meanwhile, the model was interfered with YTR. The metabolites of rats' myocardial tissue were detected in the model group, the YTR group, the sham-operation group, and the blank control group using GC-MS (8 rats in each group). Changes of metabolite contents were analyzed among different groups using principal component analysis (PCA) and least-square analysis. RESULTS: As for PCA: The results of PCA showed that principal component integral (PCI) of the four groups was mainly distributed in the three regions of oval scatterplot. The factor loading gram showed that contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, phosphoric acid, galactopyranose, lysine were changed in the model group. Analysis of partial least square method: PLS regression model showed that obvious linear correlation existed between the model group and the YTR group, which proved the model was reasonably established. The drug intervention was highly positively correlated with glycine, malic acid, glutamic acid, glucose, highly correlated with urea and butanedioic acid, but negatively correlated with lysine. According to VIP value, each variable was closely correlated with the drug intervention in sequence as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactose, tyrosine, lactic acid, and alanine. Results of variability analysis: Obvious changed variability analysis of metabolite difference showed that 10 metabolites such as glycine, etc. obviously decreased in the model group, showing significant difference when compared with the normal group (P<0.01). Compared with the model group, contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, tyrosine,urea, lactic acid, and alanine, etc. obviously increased after drug intervention (P<0.01). Of them, the increment of malic acid, glumatic acid, tyrosine, and urea was less, showing significant difference when compared with that of the normal group. The mean of lysine was slightly lowered after drug intervention, but with insignificant difference when compared with that of the model group. AMI rats of CBSS was closely correlated with myocardial metabolites such as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactopyranose, lactic acid, alanine, and tyrosine, etc. CONCLUSIONS: The metabolite profile of rats' myocardial tissue showed AMI rat model of CBSS was closely correlated with post-hypoxia glucose metabolism disorder. YTR could effectively intervene this process.

[Exploration of the research thought on the heart blood stasis syndrome].

Syndrome is the core content of Chinese medicine. It is difficult to study in the present stage. The research thoughts on the heart blood stasis syndrome were explored in this paper by disease and syndrome combination, animal models, systems biology, and medical models, and so on.

[Detection and analysis on plasma metabolomics in patient with coronary heart disease of Xin-blood stasis syndrome pattern].

OBJECTIVE: To research the plasmic metabolites and metabolic pathway of Xin-blood stasis syndrome (XBSS). METHODS: Plasma metabolic products in patients of coronary heart disease (CHD) with XBSS or non-XBSS and subjects in the control group were identified by gas chromatographic mass spectrometry (GC-MS) type QP2010, the changes of their main elements in different groups were analyzed by principal components analysis (PCA) and partial least squares (PLS) analysis. RESULTS: PCA showed that as compared with that in the control group, in the CHD-XBSS group, contents of lactic acid, beta-hydroxy butanoic acid, urea, oleic acid, octadecanoic acid and arachidonic acid were higher and that of citric acid was lower. PLS analysis showed significant difference between the control group and the other two groups, and the latter two groups tend to be of a same category. The occurrence of XBSS was positively correlated with octadecanoic acid, arachidonic acid, urea, lactic acid and beta-hydroxy, butanoic acid contents, and negatively correlated with oleic acid, L-proline, glycine, and citric acid contents. According to VIP, the degree of correlation between variables with drug interven- tion, from high to low, were ranked as arachidonic acid, octadecanoic acid, lactic acid, urea, beta-hydroxy butanoic acid, linoleic acid, glucose, alanine, oleic acid and proline. Discrepancy analysis on 11 changeful metabolites showed that the contents of arachidonic acid, octadecanoic acid, lactic acid, urea, beta-hydroxy butanoic acid and oleic acid increased in CHD patients, especially in those with XBSS (P < 0.01). In CHD patients, contents of lactic acid, beta-hydroxy butanoic acid, linoleic acid and glucose in patients of XBSS pattern were higher than in non-XBSS pattern (P < 0.01); content of linoleic acid, glucose, alanine and proline decreased in non-XBSS pattern while increased in XBSS pattern. Content of glucose in CHD-XBSS patients was significantly higher than that in the healthy control (P < 0.01). Content of citric acid was lower in CHD patients, and showed significant difference between that in CHD-XBSS patients and healthy control (P < 0.01). CONCLUSIONS: The major plasmic metabolites in CHD-XBSS patients are arachidonic acid, octadecanoic acid, lactic acid, urea, citric acid, beta-hydroxybutyric acid, oleic acid, glucose, and alanine. Analyzed from plasmic metabolite spectrum view, CHD-XBSS is related with lipid metabolism and glyco-metabolism, also with the stress induced by hypoxia and agonia.