Association between peripheral blood cells mitochondrial DNA content and severity of coronary heart disease.

BACKGROUND AND AIMS: Leukocyte mitochondrial DNA (mtDNA) content reflects the oxidant-induced cell damage, which has been observed in a wide range of cardiovascular diseases. However, whether it correlates with coronary heart disease (CHD), which closely relates to oxidative stress, has never been elucidated before. The aim of this study was to explore association between mtDNA content and the presence and severity of CHD. METHODS: The study population consisted of 400 individuals (290 with CHD and 110 controls). A quantitative real-time PCR was performed to measure the relative content of mtDNA in peripheral blood cells (PBCs). Gensini score was used to evaluate the severity of coronary stenotic lesions. An unconditional multivariate logistic regression was developed to estimate the association between CHD risk and mtDNA content by using odds ratio (OR). This study is registered with ClinicalTrials.gov, number NCT02500823. RESULTS: CHD patients, compared to controls, had lower mtDNA content (median, 0.78 vs. 0.83, p < 0.001), and mtDNA levels significantly decreased following an increasing Gensini score (p < 0.001). By using the first (highest mtDNA content) quartile of mtDNA content of controls as reference, the adjusted ORs (95% CIs) for individuals in the second, third and highest quartile of mtDNA content were 1.78 (95% CI, 1.15-3.51), 2.21 (95% CI, 1.65-3.74) and 4.83 (95% CI, 2.67-8.64), respectively (p for trend <0.001). CONCLUSIONS: These preliminary results suggest that expression of mtDNA may be associated with atherogenesis. The level of peripheral blood mtDNA in predicting the severity of coronary atherosclerosis may have a relatively certain value.

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. MATERIALS AND METHODS: In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. RESULTS: The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. CONCLUSIONS: These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.