Sirt1 hyperexpression in SHR heart related to left ventricular hypertrophy

2009 ◽  
Vol 87 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Ling Li ◽  
Lei Zhao ◽  
Wuliya Yi-Ming ◽  
Yong-Sheng Yu ◽  
Chun-Yan Xia ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Ventricular Hypertrophy ◽  
Spontaneously Hypertensive Rat ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Gene And Protein Expression

Sirt1 is a human homologue of the silent information regulator factor 2 (Sir2) and has an NAD+-dependent histone deacetylase activity. This protein is reported to have a pathogenetic role in muscle differentiation, diabetic nephropathy, and heart failure. In this study, we investigated the expression of sirt1 in spontaneously hypertensive rat (SHR) to obtain insight into the function of sirt1 in hypertensive cardiovascular hypertrophy. The gene and protein expression of sirt1 was increased in the heart in SHR compared with normotensive WKY rats. Sirt1 mRNA was not different in the aorta between SHR and WKY rats. Sirt1 mRNA expression in heart and aorta was not related to hemodynamic parameters in SHR. Hypertensive left ventricular hypertrophy was significantly and positively related to the expression of heart tissue sirt1 mRNA in SHR. Aortic hypertrophy, however, was not related to sirt1 mRNA in the aorta. The increased sirt1 protein expression was accompanied by severe cardiac hypertrophy in older SHR. These results suggest that the increase of sirt1 gene and protein expression in the heart was associated with cardiac hypertrophy.

Catecholamines, Blood Pressure, Renin and Myocardial Function in the Spontaneously Hypertensive Rat

1976 ◽  
Vol 51 (s3) ◽  
pp. 455s-459s
Author(s):  
Suzanne Oparil ◽  
Lynda Erinoff ◽  
A. Cutilletta
Keyword(s):  
Blood Pressure ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Myocardial Function ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Spontaneously Hypertensive ◽  
6 Hydroxydopamine

1. Neither nerve-growth-factor antiserum (NGFAS) administered subcutaneously nor 6-hydroxydopamine administered intraventricularly to immature spontaneously hypertensive rats (SHR) inhibited the development of the hypertensive syndrome. In contrast, NGFAS did not affect blood pressure in normotensive Kyoto/Wistar rats. 2. Peripheral vascular resistance was increased and cardiac index decreased in both NGFAS and 6-hydroxydopamine-treated SHR despite preservation of normal blood pressure. 3. NGFAS treatment did not influence the development of left ventricular hypertrophy in SHR, despite the lowering of blood pressure. In contrast, 6-hydroxydopamine caused an attenuation in the development of left ventricular hypertrophy. 4. Indices of left ventricular contractility were depressed by NGFAS treatment but not by 6-hydroxydopamine. 5. Plasma renin activity was unaffected by NGFAS treatment and increased by 6-hydroxydopamine.

scholarly journals Effect of renal denervation procedure on left ventricular hypertrophy of hypertensive rats and its mechanisms

2012 ◽  
Vol 27 (11) ◽  
pp. 815-820 ◽  
Author(s):  
Weihong Jiang ◽  
Lihua Tan ◽  
Yunzhong Guo ◽  
Xiaogang Li ◽  
Xiaohong Tang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Left Ventricular Hypertrophy ◽  
Protein Expression ◽  
Spontaneously Hypertensive Rats ◽  
Renal Denervation ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tnf Α

PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (p<0.05). In the D1 and D2 group, the LVMI, NE and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were significantly reduced (p<0.05). CONCLUSION: Renal denervation can significantly delay the progression of left ventricular hypertrophy in spontaneously hypertensive rats, which may be attributed to the not only the suppression of sympathetic activity and attenuation of pressure load but the improvement of myocardial immuno-inflammation.

Abstract 207: Differential Regulation of Ubiquitin-Proteasomal System in Right Ventricular Versus Left Ventricular Hypertrophy and Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Viswanathan Rajagopalan ◽  
Mingming Zhao ◽  
Sushma Reddy ◽  
Giovanni Fajardo ◽  
Shannamar Dewey ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Protein Expression ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Regulatory Subunit ◽  
Ubiquitinated Proteins ◽  
Gene And Protein Expression ◽  
Proteasomal Inhibition ◽  
Rv Function

Background: While the role of Ubiquitin-Proteasomal System (UPS) in left ventricular hypertrophy (LVH) and failure (LVF) has been controversial, the role of UPS in the right, RVH/RVF is unknown. Given the greater percent increase in RV mass and protein with RV vs. LV afterload stress, we hypothesized that UPS alterations could play an important role in RVH and RVF. Methods: Using our pulmonary artery constriction (PAC) model to induce RVH/RVF by 8d (n=13-14), UPS gene and protein expression, ubiquitination, oxidation (carbonylation), and enzyme activity were measured in PAC vs. sham controls. Proteasomal inhibitors epoxomicin (0.5 mg/kg/d) or MG132 (10 µg/kg/d) were administered from 1d before to 7d after surgery (n=3-6). Results: RVW/BW was increased by 109.3% in PAC mice. All mice developed progressive RV dilation, septal shift and decrease in RV function. UPS function, measured as 26S ß 5 chymotrypsin-like activity (71.3±3.9 vs. 100±8.3%; p<0.05) and 20S ß 1 caspase-like activity (66.9±3.2 vs. 100±6.9%; p<0.001), was decreased. 20S protein expression was unchanged whereas the 19S regulatory subunit Rpt5 was increased (3.3±0.5 vs. 1.4±0.2; p<0.05). UCHL1 deubiquitinase (0.3±0.04 vs. 0.05±0.004; p<0.0001) and Smurf1 E3 ubiquitin ligase (3369±538 vs. 1249±75.6; p<0.01) were increased and both poly-ubiquitinated proteins (877600±50550 vs. 639700±45050; p<0.05) and free-ubiquitins (373102±65859 vs. 177318±24188) were also increased. Carbonylation was unchanged. Pro-apoptotic Bax was increased (0.06±0.004 vs. 0.02±0.001; p<0.0001), and anti-apoptotic Bcl-2 decreased (0.2±0.03 vs. 0.5±0.08; p<0.05) with a 6-fold increase in Bax/Bcl-2 ratio. Proteasomal inhibition further increased free ubiquitin levels 2.6-fold (p<0.0001). However, neither the degree of RVH, nor decrease in RV function was altered. Conclusion: UPS has been shown to be both activated/inhibited and cardioprotective/cardiotoxic in LVH/LVF. In RVH/RVF, despite a doubling in RV mass, UPS activity is decreased, associated with increased ubiquitinated proteins and Bax/Bcl-2 ratio. Further proteasomal inhibition does not hasten RVF, suggesting that the failing RV is resistant to further proteasomal inhibition, or a limited role for the UPS in the progression from RVH to RVF.

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