The effect of metoprolol on Calpain I and CaN signaling pathway in pressure overload induced myocardial hypertrophy / 天津医药

Objective To study the mechanism of metoprolol preventing pressure overload induced myocardial hypertrophy through inhibiting calcineurin (CaN) and CalpainⅠsignaling pathway in rat model of coarctation of abdominal aorta. Methods Thirty SD rats were used for hypertension rat model induced by coarctation of suprarenal abdominal aorta. Model rats were divided into three groups, sham operation group (n=10), abdominal aortic coarctation group (n=9) and metoprolol group (n=9). The changes of blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and myocardial hypertrophy [the ratio of left ventricular mass/ body mass (LVW/BW)] were measured. RT-PCR was used to detect the expression of CaN mRNA, and Western blot assay was used to detect expressions of CaN and CalpainⅠproteins. The activity of CaN enzyme was detected and compared between three groups. Results Compared with the sham-operated sham operation group, values of SBP, DBP, LVW/BW, protein expressions and activities of CaN mRNA, CaN and CalpainⅠwere significantly increased in operation group (P<0.05). There were no significant differences in SBP and DBP between metoprolol-treated group and the operation group (P>0.05). Furthermore, values of SBP and DBP were significantly higher in metoprolol-treated group than those of sham group (P<0.05). Compared with operation group, values of LVW/BW, the protein expression and activity of CaN mRNA and Calpain Ⅰwere significantly decreased in metoprolol group (P<0.05), which were no significant differences compared with sham group. Conclusion Metoprolol prevents myocardial hypertrophy in abdominal aorta coarctative rats, through inhibiting CalpainⅠand CaN signaling pathways.

Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways / 中华心血管病杂志

<p><b>OBJECTIVE</b>Previous study showed that the signaling pathway of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)- alternative splicing of Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is related to myocardial hypertrophy. The aim of present study was to determine the effect and related mechamism of metoprolol on pressure overload induced myocardial hypertrophy.</p><p><b>METHODS</b>Pressure overload-induced hypertension was induced by coarctation of suprarenal abdominal aorta in rats. Rats were randomly divided into sham-operated control, hypertension and hypertension plus metoprolol (30 mg×kg(-1)×d(-1)) groups (n = 10 each). Blood pressure, the left ventricular weight to body weight ratio and cardiomyocytes area were measured, the protein expression of Dyrk1A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMKIIδ was detected by RT-PCR.</p><p><b>RESULTS</b>Four weeks after coarctation, cardiac hypertrophy was evidenced in rats of hypertensive group, and the protein expression of Dyrk1A was significantly upregulated, while the expression of ASF was significantly downregulated, the mRNA expression of CaMKIIδ A and B were significantly upregulated and mRNA expression of CaMKIIδ C was significantly downregulated compared to those in sham-operated control rats (all P < 0.05). Treatment with metoprolol effectively attenuated cardiac hypertrophy and reversed pressure overload induced changes on Dyrk1A and ASF, and alternative splicing of CaMKIIδ (all P < 0.05).</p><p><b>CONCLUSION</b>Metoprolol attenuates pressure overload-induced cardiac hypertrophy possibly through modulating Dryk1A-ASF-CaMKIIδ signaling pathways.</p>

Role of valsartan on myocardial Calpain I, calcineurin and Ca/calmodulin-dependent protein kinase IIδ expression of renovascular hypertensive rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To determine the protein expression of Calpain I, mRNA and protein expressions and activity of calcineurin, and the alternative splicing of Ca/calmodulin-dependent protein kinase II (CaMKII) δ in the hypertrophic heart, and to investigate the effect of angiotensin II type 1 receptor blocker valsartan (Val) on cardiac hypertrophy and the level of Calpain I, calcineurin and CaMKIIδ in renovascular hypertensive rats model.</p><p><b>METHODS</b>Rats were randomly divided into sham-operated control (n=8), hypertension (n=8) and hypertension plus Val (n=8, 30 mg×kg(-1)×(-1)). The renovascular hypertension was induced by two kidney-one clip methods in rats. The ratio of left ventricular weight to body weight was measured, the mRNA expression of calcineurin and alternative splicing of CaMKIIδ were determined by RT-PCR, the protein expression of Calpain I and calcineurin were measured by Western blot and the activity of calcineurin activity was assayed by a specialized kit.</p><p><b>RESULTS</b>Eight weeks after procedure, hypertension rats developed significantly cardiac hypertrophy, and the protein expression of Calpain I, mRNA and protein expression and the activity of calcineurin were significantly increased compared sham-operated control rats (all P<0.01), the mRNA expression of CaMKIIδA and B increased, CaMKIIδC mRNA decreased (P<0.01). Treatment with valsartan effectively attenuated cardiac hypertrophy and reversed hypertension induced changes on myocardial Calpain I, calcineurin and CaMKIIδ.</p><p><b>CONCLUSION</b>Valsartan attenuates cardiac hypertrophy in renovascular hypertensive rats, possibly through inhibiting Calpain I, calcineurin and CaMKIIδ signaling pathways.</p>

Cardiac troponin I gene mutation (Asp127Tyr) in a Chinese patient with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the disease-causing gene mutation in Chinese patients with hypertrophic cardiomyopathy and to analyze the correlation between the genotype and the phenotype.</p><p><b>METHODS</b>Specimens of peripheral blood were collected and the genome DNA was extracted in 65 unrelated patients with hypertrophic cardiomyopathy and 60 normal controls. The exon 7 and 8 of cardiac troponin I gene were screened with PCR and direct sequencing technique.</p><p><b>RESULTS</b>A missense mutation in the exon 7 of the cardiac troponin I gene was identified in a 40-year-old male patient with hypertrophic cardiomyopathy (Asp127Tyr) which was absent in the controls.</p><p><b>CONCLUSION</b>A novel missense mutation of cardiac troponin I was identified in a patient with hypertrophic cardiomyopathy, this mutation might be the disease-causing gene mutation in this Chinese patient.</p>

Role of calcineurin in the progression of cardiac hypertrophy in renovascular hypertensive rats / 生理学报

The present study was to investigate the mRNA, protein expression and the activity of calcineurin in the hypertrophic heart, and to determine the effect of calcineurin inhibitor--cyclosporine A (CsA) on the regression of cardiac hypertrophy in renovascular hypertensive rats. Renovascular hypertension was induced by two kidney-one clip methods. Two months after the operation, cardiac hypertrophy was determined by histological analysis performed in some rats (2K1C-2M), then the rats were subdivided into 2 groups: (1) 3-month old two kidney-one clip group (2K1C-3M) with rats receiving 0.9% NaCl per day for one month, and (2) CsA-treated group with rats treated with CsA for one month. Sham-operated rats were used as control. The ratio of the left ventricular weight to tibial length (LVW/TL), the area of cardiac myocyte, mRNA and protein expression and the activity of calcineurin were determined. Both the LVW/TL and the cardiomyocyte area were significantly larger in 2K1C-2M and 2K1C-3M rats than in age-matched sham-operated rats. Treatment with CsA significantly attenuated the increase in the LVW/TL as well as the cardiomyocyte area. The mRNA, protein expression and the activity of calcineurin were significantly higher in 2K1C-2M and 2K1C-3M rats than those in the age-matched sham-operated rats, while the elevation of mRNA, protein expression and activity of calcineurin were significantly suppressed in the CsA-treated rats. In conclusion, calcineurin plays a role in the progression of cardiac hypertrophy in renovascular hypertensive rats. The inhibition of calcineurin can reverse cardiac hypertrophy.