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Interplay between the cardiac renin angiotensin system and JAK-STAT signaling: role in cardiac hypertrophy,ischemia/reperfusion dysfunction,and heart failure 总被引:15,自引:0,他引:15
Recent studies have shown that the JAK-STAT signaling pathway plays a central role in cardiac pathophysiology. JAK-STAT signaling has been implicated in pressure overload-induced cardiac hypertrophy and remodeling, ischemic preconditioning, and ischemia/reperfusion-induced cardiac dysfunction. The different STAT family members expressed in cardiac myocytes appear to be linked to different, and at times, opposite responses, such as cell growth/survival and apoptosis. Thus, differential activation and/or selective inhibition of the STAT proteins by agonists for G-protein coupled receptors, such as angiotensin II, may contribute to cardiac dysfunction during ischemia and heart failure. In addition, JAK-STAT signaling may represent one limb of an autocrine loop for angiotensin II generation, that serves to amplify the actions of angiotensin II on cardiac muscle. The purpose of this article is to provide an overview of recent findings that have been made for JAK-STAT signaling in cardiac myocytes and to highlight some unresolved issues for future investigation. The central focus of this review is on recent studies suggesting that modulation or activation of JAK-STAT signaling by ANG II has pathological consequences for heart function. 相似文献
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M Pistorello M Cimolato F Pedini D Piovan M Boscaro F Fallo 《Acta endocrinologica》1992,127(3):210-214
Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10(-5), but not 10(-8) and 10(-6) mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10(-5) mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10(-5) mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells. 相似文献
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Lack of correlation between morphological index and viability as assessed by the uptake of 3H-thymidine by macrophage resident M. leprae 总被引:1,自引:0,他引:1
Thirty strains of M. leprae derived from skin biopsies of lepromatous leprosy patients were scored for Morphological Index (MI) and concurrently maintained for 2 weeks in macrophage cultures containing 3H thymidine. Selective and significant incorporation of the radioactive label was observed in cultures containing freshly extracted M. leprae as compared to control cultures with autoclaved bacilli from the same biopsy. The percentage incorporation of 3H thymidine ranged from 103 to 1140%. Morphological Index of the bacilli from these individuals varied from zero to 8. Six cultures containing bacilli with MI of less than or equal to 1 and 3 containing bacilli with MI of zero showed significant incropration of 3H thymidine. There was no correlation between the percent of solid or beaded bacilli in the inoculum and the ability of M. leprae to incorporate 3H thymidine in the macrophage cultures. 相似文献
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Renal dysfunction, as measured by the modification of diet in renal disease equations, and outcome in patients with advanced heart failure. 总被引:2,自引:0,他引:2
Roy S Gardner Kwok S Chong Eileen O'Meara Alan Jardine Ian Ford Theresa A McDonagh 《European heart journal》2007,28(24):3027-3033
AIMS: This study evaluates the prognostic utility of renal dysfunction estimated by the recently validated modification of diet in renal disease (MDRD) equations and compares it with the currently most promising predictor of prognosis in patients with advanced heart failure. METHODS AND RESULTS: We prospectively studied 182 consecutive patients with advanced chronic heart failure (CHF) referred for consideration of cardiac transplantation, with a median follow-up of 642 days. Glomerular filtration rate (GFR) was estimated using the MDRD equations and plasma taken for NT-proBNP analysis. The primary endpoint of all-cause mortality was reached in 40 patients (13.2% crude 1-year mortality), and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 44 patients. The mean GFR estimated by MDRD-1 was 58 mL/min/1.73 m(2). The median NT-proBNP concentration was 1505 (517-4014) pg/mL. Although GFR estimated by MDRD-1 was a univariate marker of all-cause mortality, the only predictor of either endpoint independent of other variables was an NT-proBNP concentration above the median. CONCLUSION: NT-proBNP appears superior to GFR estimated by MDRD in patients with advanced CHF. Moreover, NT-proBNP was able to identify patients with a poor prognosis whose GFR was already low. 相似文献
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The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a longlasting binding to the human AT1-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP > or =85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing. Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P<.05), nighttime (P<.05), and 24-h (P<.01) periods, systolic (P<.01) and diastolic (P<.05) ABP between 0 and 36 h, and both systolic (P<.001) and diastolic (P<0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P<.01), nighttime (P<.05), 24-h (P<.01), 0 to 36 h (P<.05) and during the day of missed dose (P<.05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P<.01 and <.001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose-response relationship. In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil. 相似文献