ABSTRACT. Inhibition of cardiac hypertrophy leads to a significant reduction in cardiovascular mortality and morbidity. Quercetin is by far the most abundant flavonoid and believed to ameliorate cardiovascular disease. Therefore, we investigated whether quercetin supplementation could attenuate the development of cardiac hypertrophy induced by pressure overload. Three weeks after suprarenal transverse abdominal aortic constriction, heart to body weight (HW/BW) ratio increased compared to the sham group (3.40  0.06 mg/g versus 2.83  0.02 mg/g, P<0.001). The quercetin administered group showed complete inhibition of cardiac hypertrophy (2.85  0.01 mg/g, P<0.001). Malonyldialdehyde production induced by pressure overload was suppressed by quercetin. The activities of extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase, Akt and GSK-3 were significantly increased with pressure overload and attenuated by quercetin treatment. We conclude that quercetin appears to block the development of cardiac hypertrophy induced by pressure overload in rats and that these effects may be mediated through reduced oxidant status and inhibition of ERK1/2, p38 MAP kinase, Akt and GSK-3 activities.KEY WORDS: cardiac hypertrophy, pressure overload, quercetin.J. Vet. Med. Sci. 71(6): 737-743, 2009 Cardiac hypertrophy is a homeostatic response to elevated afterload that develops due to pressure or volume overload. Although cardiac hypertrophy is a compensatory response to increased wall stress in the early stage, it is followed by decompensation and ultimately leads to heart failure if the stimulus is sufficiently intense and prolonged.Several intracellular signaling pathways including mitogen-activated protein kinase (MAPK), Janus kinase/signal transducers, activators of transcription (JAK/STAT), calcineurin [16], serine/threonine kinase, Akt and its downstream target, glycogen synthase kinase-3 (GSK-3) have been implicated in mechanical stress-induced cardiac hypertrophy. These observations have led to speculation that inhibition of these hypertrophic signals may be an effective means of clinical therapy in the treatment of pathological hypertrophy and heart failure.Quercetin (3,3',4',5,7-pentahydroxyflavone) is a member of a group of naturally occurring compounds and is one of the most widely distributed bioflavonoids [5]. Several epidemiological studies have shown a significant inverse association between dietary flavonoids and long-term mortality from coronary heart disease. A very wide range of biological actions of flavonoids, including antioxidant, antiaggregant and vasodilatory effects, support the purported role of quercetin protection against cardiovascular disease [4]. Recently, it has been reported that quercetin inhibits hypertrophy of cardiomyocytes induced by angiotensin II [15]. However, there is little information about the effect of quercetin on in vivo models of cardiac hypertrophy. Therefore, the purpose of this study is to investigate whether chronic administration of an oral daily dose of quercetin...

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Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case-control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p < 1 × 10(-8)) and rs17118 in XYLB gene located on chromosome 3p21 (p < 1 × 10(-6)) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR = 2.02, 95 % CI = 1.35-3.03) or rs17118 AA genotype (OR = 1.50, 95 % CI = 1.17-1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR = 2.78, 95 % CI = 1.59-4.86) and in individuals without diabetes (OR = 1.93, 95 % CI = 1.27-2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR = 1.73, 95 % CI = 1.08-2.78) and for individuals without diabetes (OR = 1.52, 95 % CI = 1.17-1.98) or non-smoker (OR = 1.59, 95 % CI = 1.16-2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.

Aims: Perioperative stroke remains a devastating complication after transcatheter aortic valve implantation (TAVI), using cerebral embolic protection device (CEPD) during TAVI may reduce stroke rate according to some studies. Therefore, we conducted this meta-analysis and may suggest whether CPED should be routinely used during TAVI. Methods and results: Studies were included which compared the outcome of stroke when with or without CEPD during TAVI, random controlled trials (RCTs) only, and followed up for at least 30 days. The primary end point was stroke. The risk of stroke at 30-days was no significantly difference in using CEPD during TAVI compared with control: RR 0.84, 95% CI 0.63 to 1.12, p = 0.23, I2=9%. Subgroup analysis was conducted according to the type of CEPD. There were no significantly differences neither using I&LCCA type nor TMCA type compared with control: RR 0.69, 95% CI 0.47 to 1.00, p = 0.05, I2=25%; RR 1.16, 95% CI 0.74 to 1.83, p = 0.51, I2=0%. Conclusions: In this meta-analysis, there was no significant evidence indicated CEPD can reduce the risk of stroke risk during TAVI. However, subgroup analysis of I&LCCA type group P=0.05, according to the basis of the 95% CI around this outcome, it is hard to rule out the efficacy of CEPD during TAVI. Maybe with large sample size, one valve type only, one outcome definition only, multicenter studies and extend the retention time of CEPD, the efficacy of CEPD would be proofed.

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