Metabolic mechanism and intervention strategy of atrial fibrillation in the elderly / 生理学报

Atrial fibrillation (AF) is a cardiovascular epidemic that occurs primarily in the elderly with primary cardiovascular diseases, leading to severe consequences such as stroke and heart failure. The heart is an energy-consuming organ, which requires a high degree of metabolic flexibility to ensure a quick switch of metabolic substrates to meet its energy needs in response to physiological and pathological stimulation. Metabolism is closely related to the occurrence of AF, and AF patients manifest metabolic inflexibility, such as insulin resistance and the metabolic shift from aerobic metabolism to anaerobic glycolysis. Moreover, our research group and the others have shown that metabolic inflexibility is a crucial pathologic mechanism for AF. Energy metabolism is closely linked to the aging process and aging-related diseases, and impaired metabolic flexibility is considered as an essential driver of aging. Therefore, this review focuses on the alteration of metabolic flexibility in the elderly and reveals that impaired metabolic flexibility may be an important driver for the high prevalence of AF in the elderly, hoping to provide intervention strategies for the prevention and treatment of AF in the elderly.

Active components and action mechanism of Shenmai Injection in treatment of atrial fibrillation based on network pharmacology and molecular docking / 中国中药杂志

This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.

Arginine vasopressin stimulates proliferation of adult rat cardiac fibroblasts via protein kinase C-extracellular signal-regulated kinase 1/2 pathway / 生理学报

Arginine vasopressin (AVP), a neurohormone and hemodynamic factor implicated in the pathophysiology of hypertension and congestive heart failure, can also act as a growth-stimulating factor. Our previous work demonstrated that AVP is a mitogen for neonatal rat cardiac fibroblasts (CFs). In the present study, we extended our investigations to adult rat CFs to explore whether AVP could induce adult rat CF proliferation and, if so, to identify the mechanism involved. Adult rat CFs were isolated, cultured and subjected to AVP treatment. DNA synthesis and cell cycle distribution were analyzed by [(3)H]-thymidine incorporation and flow cytometry. Cellular extracellular signal-regulated kinase 1/2 (ERK1/2) activity was measured by in vitro kinase assay using myelin basic protein (MBP) as a substrate. Protein expressions of total- and phospho-ERK1/2, p27(Kip1), cyclins D1, A, E were assessed by Western blot. The results showed that AVP stimulated DNA synthesis in adult rat CFs, and the effect was abolished by a V1 receptor antagonist, d(CH(2))(5)[Tyr(2)(Me), Arg(8)]-vasopressin (0.1 μmol/L), but not by a V2 receptor antagonist, desglycinamide-[d(CH(2))(5), D-Ile(2), Ile(4), Arg8]-vasopressin (0.1 μmol/L). AVP induced an activation of ERK1/2, which could be mimicked by the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA, 30 nmol/L, 5 min), but abolished by depletion of PKC via chronic PMA incubation (2.5 μmol/L, 24 h). In addition, AVP down-regulated protein expression of p27(Kip1), increased protein expressions of cyclins D1, A and E, and induced cell cycle progression from G(0)/G(1) into S stage. Inhibition of ERK1/2 activation by PD98059 (30 μmol/L) abolished the effect of AVP on DNA synthesis, protein expressions of p27(Kip1), cyclins D1, A and E as well as cell cycle progression. These results suggest that AVP is also a growth factor for adult rat CFs. The mitogenic effect of AVP is mediated via V1 receptors and PKC-ERK1/2 pathway. Moreover, AVP modulates the expressions of cell cycle regulatory proteins p27(Kip1) and cyclins D1, A and E, which lie downstream of ERK1/2 activation, and induces cell cycle progression in adult rat CFs.

The Role of Transforming Growth Factor-?_1 in the Proliferation of Cardiac Fibroblasts Induced by Chymase / 中华高血压杂志

Objective To investigate the effect of chymase on the proliferation of rat cardiac fibroblasts (CFs) and the role of transforming growth factor-?1 (TGF-?_1).Methods Cultured CFs of neonatal SD rats were isolated by trypsinization.Cell number and DNA synthesis were evaluated by MTT assay (A_(490) value) and [~3H]-deoxythy- midine [~3H]-TdR incorporation.The mRNA expression of TGF-?_1 in CFs was determined by RT-PCR.Results Chymase increased CFs numbers and [~3H]-TdR incorporation in a dose-dependent manner.The A_(490) value of CFs stimulated by 15,30 and 60 ng/mL chymase was 0.263?0.033,0.348?0.031 and 0.387?0.026,respectively, which were all significantly higher than that of control (0.201?0.019,P

Study on the relationship between passive smoking and blood lipids, fibrinogen and viscosity among women who never smoke / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine whether blood lipids profile, fibrinogen and viscosity were associated with passive smoking (i. e. environmental tobacco smoke, ETS) in Chinese women who never smoke.</p><p><b>METHODS</b>In Xi'an, China, a case-control study was carried out on 115 cases of coronary heart disease (CHD) defined by coronary arteriography (CAG) and 208 non-CHD controls confirmed by CAG and/or exercise electrocardiography. Data on exposure to ETS, defined as exposure from cigarettes smoking husband or co-workers or both for at least 5 years, was obtained through standardized interviews. Standard laboratory methods were used and the lipid measurements were under US CDC quality control programs.</p><p><b>RESULTS</b>In the subjects defined by CAG, the levels of high density lipoprotein cholesterol (HDL-C), HDL2C, apolipoprotein (apo) A1 among passive smokers appeared lower than those in non-passive smokers,but the low density lipoprotein cholesterol (LDL-C), apoB, apoB/A1, fibrinogen, plasma and whole blood viscosity were higher than that in non-passive smokers. There were positive associations of the numbers of coronary arteriosclerosis with the levels of blood lipids,fibrinogen and viscosity. In the non-CHD controls, 81 subjects were not exposed and 127 were exposed to ETS. The P values of t-test for the adjusted (for age, body mass index, present diseases history) means between two groups were listed below: 0.06 (total cholesterol), 0.30 (triglyceride), 0.004 (HDL-C), <0.001 (HDL2-C), < 0.001 (apoA1), 0.009 (apoB), <0.001 (apoB/apoA1), <0.001 (fibrinogen), <0.001 (plasma viscosity), <0.001 and 0.004 [two measures (5.75/s and 230/s) of whole blood viscosity]. The correlation coefficients between cumulative exposure of passive smoking and HDL-C,HDL2-C,apoA1, apoB, apoB/apoA1, fibrinogen, plasma viscosity, and two measures of whole blood viscosity were -0.25, -0.27, -0.30, 0.24, 0.31, 0.32, 0.43, 0.51 and 0.36 (all P<0.01), respectively.</p><p><b>CONCLUSION</b>Passive smoking could affect blood lipid metabolism, fibrinogen and viscosity in the never smoking women which might contribute to the causation of coronary heart disease.</p>

Inhibitory effect of cyclosporin A on growth and collagen synthesis of rat cardiac fibroblasts induced by arginine vasopressin / 药学学报

<p><b>AIM</b>To investigate the effects of cyclosporin A (CsA) on growth and collagen synthesis of cardiac fibroblasts (CFs) induced by arginine vasopressin (AVP).</p><p><b>METHODS</b>CFs of neonatal Sprague-Dawley rats were isolated by trypsinization and cultured; growth-arrested CFs were stimulated with 1 x 10(-7) mol x L(-1) AVP in the presence or absence of CsA (0.05, 0.5 and 5 micromol x L(-1)). MTT and flow cytometry techniques were adopted to measure cell number and analyze cell cycle respectively. Collagen synthesis was determined by measurement of hydroxyproline content in culture supernatant with colorimetry. Calcineurin activity was estimated by chemiluminescence. Trypan blue staining to test the viability of CFs.</p><p><b>RESULTS</b>0.05, 0.5 and 5 micromol x L(-1) CsA inhibited the increase of CFs number induced by 1 x 10(-7) mol x L(-1) AVP in a dose-dependent manner, with the inhibitory rates by 12%, 24% and 29%, respectively (P < 0.05). Furthermore, cell cycle analysis showed 0.5 micromol x L(-1) CsA decreased the S stage percentage and proliferation index of CFs stimulated by AVP (P < 0.05). In culture medium, the hydroxyproline content induced by AVP decreased by 0.5 and 5 micromol x L(-1) CsA (P < 0.05), with the inhibitory rates of 29% and 33%, respectively. CsA completely inhibited the increment of calcineurin activity induced by AVP (P < 0.01), but CsA itself had no effect on the baseline of calcineurin activity and CFs viability.</p><p><b>CONCLUSION</b>CsA inhibits proliferation and collagen synthesis of CFs by virtue of blocking calcineurin signaling pathway and might provide a novel target for prevention and treatment to cardiac fibrosis.</p>

Arginine vasopressin-induced nitric oxide content changes in cultured cardiac fibroblasts and its relation to nuclear factor-kappaB / 生理学报

To investigate the changes in the nitric oxide (NO) contents, nitric oxide synthase (NOS) activity and inducible nitric oxide (iNOS) mRNA expression in arginine vasopressin (AVP)-induced cardiac fibroblasts (CFs) in vitro and its relation to nuclear factor-kappaB (NF-kappaB), CFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence-interactive laser cytometer techniques and Western blotting were used respectively to detect NO contents, NOS activity, iNOS mRNA expression and the activation of NF-kappaB in CFs. AVP increased NO contents, NOS activity and iNOS mRNA expressions in a concentration-dependent manner; NF-kappaB was activated and mobilized from cytoplasm to nucleus in AVP-induced CFs; PDTC, one of the inhibitors of NF-kappaB, could inhibit aforementioned increments. It is suggested that the increases in NO contents, elevation of NOS activity and increment of iNOS mRNA expression may be mediated through NF-kappaB activation pathway in cultured CFs induced by AVP, and that NF-kappaB is involved in the occurrence and development of myocardial fibrosis.