Ventricular remodeling is a milestone in the progression of congestive heart failure (CHF), which is characterized by cardiomyocyte hypertrophy, apoptosis, and remodeling of the extracellular matrix (ECM). During cardiac hypertrophy transition to heart failure, the composition and types of collagen undergo complex alterations due to neurohormonal disturbance and local cytokine release. CHF is a process of systemic inflammation with overexpression of local inflammatory cytokines including tumor necrosis factor (TNF)-a, interleukin-1 (IL-1) b and matrix metalloproteinases (MMPs). Those inflammatory cytokines may play a crucial role in the development of heart failure. 1)Recent clinical trials and experimental studies have provided evidence to suggest that increased cardiac TNF-a expression contributes to the progress of left ventricle (LV) dysfunction.2,3) Experimental studies showed that increased TNF-a levels could cause LV remodeling and promote the deterioration of LV function. 4,5) MMPs constitute a family of zinc-dependent enzymes that are responsible for ECM degradation in either a physiological or pathological process.6) Myocardial ECM remodeling regulated by MMPs is implicated in the progression of heart failure. Recent reports have shown TNF-a contributes to the process of myocardial remodeling in evolving heart failure through the local induction of specific MMPs. [5][6][7][8] Modification of the expression of TNF-a and MMPs may serve as potential therapeutic targets in the treatment of heart failure.Curcumin is a polyphenol contained in the rhizome of the plant Curcuma longa Linn. Previous studies demonstrated that curcumin is an effective cell protector with antiinflammatory, antioxidizant and antifibrotic effects. It can inhibit the expression of a sequence of inflammatory cytokines such as TNF-a, IL-1, or IL-8 9) and MMP-3, MMP-13, 10) MMP-2 11) in the kidney or derma. Curcumin is a potential cleanser of oxidized free radicals (OFRs) and this effect is much stronger than that of carotene or vitamin E 12) due to its ability to suppress the synthesis of xanthine oxidase and lower its activity, 13) but to enhance the activity of the superoxide dismutase (SOD) enzyme.14) Curcumin can retard the fibrotic process in the lung, 15) liver, or kidney.16) It is proposed that this effect is associated with down-regulation of TNF-a expression, reducing lipid peroxidization and blocking the transmission of apoptotic signals.16) Curcumin suppresses renal parenchymal cell apoptosis in mice in which the lateral ureter was ligated to inhibit activation of nuclear transcription factor (NF)-kB and down-regulate the expression of Fas-ligand.In the present study, we tested the hypothesis that curcumin could improve cardiac function and counteract myocardiac collagen remodeling of failing hearts. We also explored the influence of curcumin on the expression of TNF-a and MMP-2 in the LV myocardium of pressure overloaded rabbits. Objective: Curcumin is a wide-spectrum cellular protector with antiinflammatory, antioxidizant, ...
The aim of the present study was to investigate the effect of coronary artery angioplasty on the recruitment of circulating endothelial progenitor cells (EPCs) in patients with angina pectoris. A total of 66 patients treated by coronary stenting were enrolled in the PCI group and 17 patients that underwent angiography alone were enrolled in the control group. The EPC count in the blood was measured by flow cytometry prior to and at 1, 3, 5, 7 and 24 h following angioplasty in the percutaneous coronary intervention (PCI) group, and at three time-points following angiography in the control group. Differences between the two groups included the characteristics of the coronary artery lesions, the incidence of diabetes and family history of coronary heart disease. The mean surface area of the stent deployed was 335.59±234.99 mm. No significant change in EPC count was measured in the control group. In the PCI group, a moderate and delayed increase in the number of cluster of differentiation (CD)34/kinase domain receptor (KDR) EPCs occurred at 24 h post-balloon inflation compared with the baseline level. The CD133/CD34/KDR subpopulations showed undulating changes at 3, 7 and 24 h post-PCI (P=0.016, P=0.01 and P=0.032, respectively). An arch shape was displayed in CD133/KDR cells; initially, a reduction occurred at 3 h and was maintained constantly until 7 h (P=0.003, P=0.013 and P=0.033 at 3, 5 and 7 h, respectively), after which a slight increase to the baseline level occurred at 24 h (P=0.084). The CD133/CD34 cells increased in stepwise manner until 24 h. The CD34/KDR EPC change magnitude correlated significantly with a global damage index by partial correlation analysis (P<0.001). The results suggested that a time-dependent mobilization of EPCs may be initiated by PCI; the change magnitude of the CD34/KDR cells was associated particularly with endothelial injury degree from the PCI procedure.
Background To assess the effects of telmisartan on susceptibility of atrial fibrillation (AF) in pressure overload rats, and to probe the underlying molecular mechanism and signal pathways. Methods Forty-nine 12-week-old male SD rats were randomly divided into sham operation (n = 15), abdominal aorta coarctation (AAC, n = 17), and AAC with telmisartan treatment groups (n = 17). Telmisartan 10 mg/(kg d) was administered by gavage for 4 weeks after AAC. Four weeks after operation, the indexes of echocardiography, hemodynamics, and cardiac electrophysiology including left atrial conduction time (LACT) and interatrial conduction time (IACT) were assessed. The mRNAs were extracted from left atrial tissues and analyzed by next generation sequencing. Results Systolic left ventricular pressure, systolic aortic pressure, left atrial diameters, and interventricular septal thickness in AAC rats were higher than those in sham rats (all P < 0.05), all of which were lowered by telmisartan treatment (all P < 0.05). LACT and IACT were significantly increased in AAC rats and ameliorated by telmisartan treatment. In isolated perfused heart, duration of AF induced by burst electrical stimulation was longer in AAC rats, which was shortened by telmisartan treatment. A total of 897 genes were downregulated by AAC but upregulated by telmisartan treatment (down/up 897 gene set). Also, 1,542 genes were upregulated by AAC but downregulated by telmisartan treatment (up/down 1,542 gene set). Venn and GO enrichment analyses showed that 5 target genes in the down/up 897 gene set were the key rate limiting enzymes of fatty acid oxidation while 5 target genes in the up/down 1,542 gene set were involved in Wnt/β-catenin signal pathway and type I and II collagen components. Conclusions Telmisartan lowers AF susceptibility via suppressing the left atrial enlargement and shortening atrial conduction time. Possible molecular mechanisms may be related to the improvement of fatty acid oxidation and downregulation of the Wnt/β-catenin pathway and collagen expression.
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