Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP/protein kinase G signaling in cardiac fibroblasts.

BACKGROUND: Omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) from fish oil ameliorate cardiovascular diseases. However, little is known about the effects of ω-3 polyunsaturated fatty acids on cardiac fibrosis, a major cause of diastolic dysfunction and heart failure. The present study assessed the effects of ω-3 polyunsaturated fatty acids on cardiac fibrosis. METHODS AND RESULTS: We assessed left ventricular fibrosis and pathology in mice subjected to transverse aortic constriction after the consumption of a fish oil or a control diet. In control mice, 4 weeks of transverse aortic constriction induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation into myofibroblasts). Dietary supplementation with fish oil prevented transverse aortic constriction-induced cardiac dysfunction and cardiac fibrosis and blocked cardiac fibroblast activation. In heart tissue, transverse aortic constriction increased active transforming growth factor-ß1 levels and phosphorylation of Smad2. In isolated adult mouse cardiac fibroblasts, transforming growth factor-ß1 induced cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid increased cyclic GMP levels and blocked cardiac fibroblast transformation, proliferation, and collagen synthesis. Eicosapentaenoic acid and docosahexaenoic acid blocked phospho-Smad2/3 nuclear translocation. DT3, a protein kinase G inhibitor, blocked the antifibrotic effects of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid and docosahexaenoic acid increased phosphorylated endothelial nitric oxide synthase and endothelial nitric oxide synthase protein levels and nitric oxide production. CONCLUSION: Omega-3 fatty acids prevent cardiac fibrosis and cardiac dysfunction by blocking transforming growth factor-ß1-induced phospho-Smad2/3 nuclear translocation through activation of the cyclic GMP/protein kinase G pathway in cardiac fibroblasts.

Antifibrotic effects of ω-3 fatty acids in the heart: one possible treatment for diastolic heart failure.

Half of heart failure patients have diastolic heart failure, which has no effective treatments. Several studies indicate a role for ω-3 polyunsaturated fatty acids (PUFAs) in heart failure. Recent studies suggest that ω-3 PUFAs inhibit cardiac fibrosis and attenuate diastolic dysfunction. This opens up possible new avenues for treatment of diastolic heart failure. In this review, we focus on the antifibrotic effects of ω-3 PUFAs in heart and the underlying cellular and molecular mechanisms.

Eplerenone prevents adverse cardiac remodelling induced by pressure overload in atrial natriuretic peptide-null mice.

1. Atrial natriuretic peptide (ANP)-null mice (Nppa(-/-)) exhibit cardiac hypertrophy at baseline and adverse cardiac remodelling in response to transverse aortic constriction (TAC)-induced pressure overload stress. Previous studies have suggested that natriuretic peptides could potentially oppose mineralocorticoid signalling at several levels, including suppression of adrenal aldosterone production, inhibition of mineralocorticoid receptor (MR) activation or suppression of MR-mediated production of pro-inflammatory factors. Thus, we hypothesized that the MR blocker eplerenone would prevent the exaggerated left ventricular (LV) remodelling/fibrosis and dysfunction after TAC in Nppa(-/-). 2. In the present study, Nppa(-/-) and wild-type Nppa(+/+) mice fed eplerenone- or vehicle (oatmeal)-supplemented chow since weaning were subjected to TAC or sham operation. The daily dose of eplerenone administered was approximately 200 mg/kg. At 1 week after TAC, LV size and function were evaluated by echocardiogram and LV cross-sections were stained with picrosirius red for collagen volume measurement. Total RNA was extracted from the LV for real-time polymerase chain reaction analysis of osteopontin. 3. Eplerenone had no effect on baseline hypertrophy observed in sham-operated Nppa(-/-) compared with Nppa(+/+) mice. Eplerenone attenuated the TAC-induced increase in LV weight in both genotypes and completely prevented LV dilation, systolic dysfunction and interstitial collagen deposition seen in Nppa(-/-) mice after TAC. However, serum aldosterone levels were lower in Nppa(-/-) compared with Nppa(+/+) wild types. No interaction between eplerenone and genotype in osteopontin mRNA levels was observed. 4. Eplerenone prevents adverse cardiac remodelling related to pressure overload in ANP-deficient mice, mainly due to an antifibrotic effect. The mechanism whereby ANP deficiency leads to excess hypertrophy, fibrosis and early failure following TAC is increased profibrotic signals resulting from excess or unopposed MR activation, rather than increased levels of aldosterone.

Effects of electroacupuncture plus intra-carotid drug injection on rheoencephalogram in patients with cerebral infarction.

PURPOSE: To investigate the mechanism of electroacupuncture (EA) plus intra-carotid drug injection for treating cerebral infarction. METHODS: Rheoencephalogram was recorded with a RG-2B type of bridge rheoencephalograph and findings were compared before and after the treatment. RESULTS: After the treatment, the prolonged rising time was shortened, and the decreased amplitude obviously elevated. CONCLUSION: The therapy can dilate cerebral blood vessels, increase the cerebral blood flow, and improve the elasticity of cerebral blood vessels, leading to sufficient blood and oxygen supply in the ischemic brain tissues and to restoration of their functions.

Clinical observation on treatment of rheumatoid arthritis with fengshi xiandan in 53 cases.

We have successfully developed Fengshi Xiandan ([symbol: see text]) and used it to treat 53 cases of rheumatoid arthritis (RA), with indomethacin used to treat another 53 cases of RA as the controls. The results showed that the rate of cure and obvious effect was 54.7% and the total effective rate was 92.4% in the treatment group, as compared to 26.4% and 66.0% respectively in the control group, with an obvious difference in curative effect between the two groups (P < 0.01). The improvement of all the main clinical symptoms and signs except arthralgia in the treatment group was superior to that in the control group (P < 0.05 or P < 0.01). The improvement of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reaction protein (CRP), immunoglobulin (Ig), T-lymphocyte subgroups, micro-circulation in nail fold, and red blood cell (RBC) and hemoglobin (Hb) of anemia patients in the treatment group was superior to that in the control group (P < 0.05 or P < 0.01). There was an obvious difference (P < 0.05 or P < 0.01) in superoxide dismutase (SOD) of RBC and lipid peroxide (LPO) of plasma before treatment in the two groups as compared to normal group (P < 0.05 or P < 0.01). The level of SOD and LPO after treatment in the treatment group obviously tended to normal as compared to that before treatment (P < 0.05 or P < 0.01). The reduction of LPO in the treatment group was obviously superior to that in the control group (P < 0.01). The result shows that Fengshi Xiandan ([symbol: see text]) with an obvious curative effect on RA can not only control the symptoms of RA but also improve its pathologic damage and prevent its development.