eNOS Deficient Mice Develop Progressive Cardiac Hypertrophy with Altered Cytokine and Calcium Handling Protein Expression

2007 ◽  
Vol 7 (3) ◽  
pp. 165-177 ◽  
Author(s):  
Michael P. Flaherty ◽  
Maria Brown ◽  
Ingrid L. Grupp ◽  
Jo El Schultz ◽  
Sidney S. Murphree ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Calcium Handling ◽  
Deficient Mice

scholarly journals AKAP13 Rho-GEF and PKD-Binding Domain Deficient Mice Develop Normally but Have an Abnormal Response to β-Adrenergic-Induced Cardiac Hypertrophy

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62705 ◽  
Author(s):  
Matthew J. Spindler ◽  
Brian T. Burmeister ◽  
Yu Huang ◽  
Edward C. Hsiao ◽  
Nathan Salomonis ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Binding Domain ◽  
Abnormal Response ◽  
Rho Gef ◽  
Deficient Mice

Abstract 370: Upregulation of Renal D5 Dopamine Receptor Ameliorates Hypertension in D3 Deficient Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Xiaoyan Wang ◽  
Crisanto S Escano ◽  
Laureano Asico ◽  
John E Jones ◽  
Alan Barte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Deficient Mice

D 3 dopamine receptor (D 3 R) deficient mice have renin-dependent hypertension but the hypertension is mild and is not associated with oxidative stress. In order to determine if any compensatory mechanism in the kidney is involved in the regulation of blood pressure with disruption of D 3 R, we measured the renal protein expression of dopamine receptors in D 3 R homozygous (D 3 -/-) and heterozygous (D 3 +/-) knockout mice and their wild type (D 3 +/+) littermates. D 5 dopamine receptor (D 5 R) (169±23%, reported as % of D 3 +/+, n=5/group) expression was increased but D 4 dopamine receptors protein expression (59±8%) was decreased, while no significant changes were found with D 1 and D 2 dopamine receptors. Immunocytochemistry showed a stronger renal staining of D 5 R but without a change in renal tubule cell distribution in D 3 -/- relative to D 3 +/+ mice. D 5 R abundance was also increased in D 3 +/- (205±30%, n=5/group) relative to D 3 +/+ mice, while D 1 R abundance was similar between D 3 +/- and D 3 +/+ mice. The increase in D 5 R expression was abolished while blood pressure was increased further in D 3 -/- mice fed a high salt diet. Treatment of the D 1 -like (including D 1 and D 5 receptors) antagonist, SCH23390 , increased the blood pressure to a greater extent in anesthetized D 3 -/- mice than in D 3 +/+ mice (n=4/group), suggesting that the upregulation of D 5 R may modulate the hypertension in mice caused by the disruption of D 3 R. Since dopamine inhibits the NADPH oxidase-induced production of reactive oxygen species (ROS) via the D 5 R, we also measured the protein expression of NOXs in the kidney and isoprostane in the urine. No NADPH oxidase subunit was increased in D 3 -/- and D 3 +/- mice relative to D 3 +/+ mice fed a normal or salt high salt diet, and urinary isoprostane excretion was also similar in D 3 -/- and D 3 +/+ mice. Our findings suggest that the upregulation of D 5 R may minimize the hypertension and prevent oxidative stress in D 3 -/- mice.

Abstract P173: Role Of Potassium Intake On Hypertensive Cardiovascular Damage In Apolipoproteine-deficient Mice Under Normal And High Salt Conditions

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Mina Yakoub ◽  
Denada Arifaj ◽  
Doron Argov ◽  
Masudur Rahman ◽  
Sebastian Temme ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Aortic Arch ◽  
High Salt ◽  
Ang Ii ◽  
Cardiac Damage ◽  
High Sodium ◽  
Cardiovascular Damage ◽  
High K ◽  
Deficient Mice

Reduced potassium (k+) intake has been linked to cardiovascular diseases. The underlying mechanisms remain unknown. Here, we investigate the effect of low (0%), normal (0.5%) and high K+ (5%) diet on the development of atherosclerosis and hypertensive cardiac damage. To induce atherosclerosis, apolipoprotein-deficient mice were infused with angiotensin (Ang) II (500ng/kg/min) for 28 days. Potassium treatment was initiated 2 weeks before Ang II infusion. Cardiac function was assessed by MRI. Levels of K+ in the serum and urine were significantly different between groups. The Ang II infused mice from the K+ low group had significantly higher atherosclerotic plaques in the aortic arch (21±3%) compared to K+ high (10±2%) and K+ normal (11±2%) groups. The atherosclerosis development was blood pressure independent since no differences in blood pressure between the groups were observed. Although heart to body-weight ratio did not differ between three groups, K+ low diet was associated with a lower ejection fraction rate and increased mRNA expression levels of cardiac ANP, BNP, collagen and fibronectin compared to the K+ normal and K+ high group. After Ang II infusion, assessment of aldosterone levels in urine showed significant higher aldosterone levels in the high K+ (214±72ng/24h) compared to normal K+ (26±6ng/24h) and low K+ (18±4ng/24h) groups. Aldosterone induced cardiovascular damage is known to be aggravated by sodium. To, evaluate whether high sodium diet unmask aldosterone mediated cardiovascular damage in the high K+ group, mice fed a high or normal K+ diet were additionally treated with high sodium (1% NaCl) in the drinking water. During Ang II treatment, high salt diet accelerated atherosclerosis in the aortic arch of both groups but no differences were observed between the high K+ high/high Na+ (41±7%) and normal K+/high Na+ (49±2%) group. In contrast, high K+/high Na+ group have significantly more severe cardiac hypertrophy compared to normal K+ high Na+ group (8.9±0.7 vs 6.4±0.7mg/g). These results were confirmed by MRI. K+ deficient diet induces atherosclerosis and cardiac damage during Ang II induced hypertension. K+ enriched diet exacerbates cardiac hypertrophy only under high Na+ conditions most likely in an aldosterone-dependent mechanism.

scholarly journals LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Improves Cardiac Hypertrophy and Fibrosis and Cardiac Lymphatic Remodeling in Transverse Aortic Constriction Model Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ge ◽  
Li Zhao ◽  
Chen Liu ◽  
Xiaoming Ren ◽  
Yi-hui Yu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Mouse Heart ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Expression Levels ◽  
Factor C ◽  
Proinflammatory Factors

Cardiac hypertrophy and ventricular remodeling following heart failure are important causes of high mortality in heart disease patients. The cardiac lymphatic system has been associated with limited research, but it plays an important role in the improvement of myocardial edema and the promotion of fluid balance. LCZ696 is a novel combination of angiotensin and neprilysin inhibitors. Here, we studied the role played by LCZ696 during transverse aortic constriction (TAC) induced cardiac hypertrophy and changes in the lymphatic system. Mice undergoing aortic coarctation were constructed to represent a cardiac hypertrophy model and then divided into random groups that either received treatment with LCZ696 (60 mg/kg/d) or no treatment. Cardiac ultrasonography was used to detect cardiac function, and hematoxylin and eosin (H&E) and Masson staining were used to detect myocardial hypertrophy and fibrosis. The proinflammatory factors interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were detected in the blood and heart tissues of mice. The protein expression levels of lymphatic-specific markers, such as vascular endothelial growth factor C (VEGF-C), VEGF receptor 3 (VEGFR3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were detected in mouse heart tissues. We also examined the colocalization of lymphatic vessels and macrophages by immunofluorescence. The results showed that LCZ696 significantly improved heart dysfunction, cardiac hypertrophy, and fibrosis and inhibited the expression of proinflammatory factors IL-6, IL-1β, and TNF-α in the circulating blood and heart tissues of mice. LCZ696 also decreased the protein expression levels of VEGF-C, VEGFR3, and LYVE-1 in mouse heart tissues, ameliorated the transport load of lymphatic vessels to macrophages, and improved the remodeling of the lymphatic system in the hypertrophic cardiomyopathy model induced by TAC.

Role of myofibrillogenesis regulator-1 in myocardial hypertrophy

2006 ◽  
Vol 290 (1) ◽  
pp. H279-H285 ◽  
Author(s):  
Xiuhua Liu ◽  
Tianbo Li ◽  
Sheng Sun ◽  
Feifei Xu ◽  
Yiguang Wang
Keyword(s):  
Rna Interference ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Western Blotting ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Homologous Gene ◽  
Ang Ii ◽  
Rat Cardiomyocytes

Myofibrillogenesis regulator-1 (MR-1) is a novel homologous gene, identified from a human skeletal muscle cDNA library, that interacts with contractile proteins and exists in human myocardial myofibrils. The present study investigated MR-1 protein expression in hypertrophied myocardium and MR-1 involvement in cardiac hypertrophy. Cardiac hypertrophy was induced by abdominal aortic stenosis (AAS) in Sprague-Dawley rats. Left ventricular (LV) hypertrophy was assessed by the ratio of LV wet weight to whole heart weight (LV/HW) or LV weight to body weight (LV/BW). Rat MR-1 (rMR-1) expression in the myocardium was detected by immunohistochemical and Western blotting analysis. Hypertrophy was induced by ANG II incubation in cultured neonatal rat cardiomyocytes. The effect of rMR-1 RNA interference on ANG II-induced hypertrophy was studied by transfection of cardiomyocytes with an RNA interference plasmid, pSi-1, which targets rMR-1. Hypertrophy in cardiomyocytes was assessed by [3H]Leu incorporation and myocyte size. rMR-1 protein expression in cardiomyocytes was detected by Western blotting. We found that AAS resulted in a significant increase in LV/HW and LV/BW: 89% and 86%, respectively ( P < 0.01). Immunohistochemistry and Western blot analysis demonstrated upregulated rMR-1 protein expression in hypertrophic myocardium. ANG II induced a 24% increase in [3H]Leu incorporation and a 65.8% increase in cell size compared with control cardiomyocytes ( P < 0.01), which was prevented by treatment with losartan, an angiotensin (AT1) receptor inhibitor, or transfection with pSi-1. rMR-1 expression increased in ANG II-induced hypertrophied cardiomyocytes, and pSi-1 transfection abolished the upregulation. These findings suggest that MR-1 is associated with cardiac hypertrophy in rats in vivo and in vitro.

scholarly journals Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Jianyong Qi ◽  
Qin Liu ◽  
Kaizheng Gong ◽  
Juan Yu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Study Groups ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Cardioprotective Effects

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy.Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot.Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P<0.05).Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy

2006 ◽  
Vol 291 (4) ◽  
pp. H1545-H1553 ◽  
Author(s):  
Jyothish B. Pillai ◽  
Madhu Gupta ◽  
Senthilkumar B. Rajamohan ◽  
Roberto Lang ◽  
Jai Raman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cell Signaling ◽  
Primary Cultures ◽  
Heart Weight ◽  
Cell Protein ◽  
Sequence Of Events ◽  
Deficient Mice

Poly(ADP-ribose) polymerase-1 (PARP), a chromatin-bound enzyme, is activated by cell oxidative stress. Because oxidative stress is also considered a main component of angiotensin II-mediated cell signaling, it was postulated that PARP could be a downstream target of angiotensin II-induced signaling leading to cardiac hypertrophy. To determine a role of PARP in angiotensin II-induced hypertrophy, we infused angiotensin II into wild-type (PARP+/+) and PARP-deficient mice. Angiotensin II infusion significantly increased heart weight-to-tibia length ratio, myocyte cross-sectional area, and interstitial fibrosis in PARP+/+ but not in PARP−/− mice. To confirm these results, we analyzed the effect of angiotensin II in primary cultures of cardiomyocytes. When compared with PARP−/− cardiomyocytes, angiotensin II (1 μM) treatment significantly increased protein synthesis in PARP+/+ myocytes, as measured by 3H-leucine incorporation into total cell protein. Angiotensin II-mediated hypertrophy of myocytes was accompanied with increased poly-ADP-ribosylation of nuclear proteins and depletion of cellular NAD content. When cells were treated with cell death-inducing doses of angiotensin II (10–20 μM), robust myocyte cell death was observed in PARP+/+ but not in PARP−/− myocytes. This type of cell death was blocked by repletion of cellular NAD levels as well as by activation of the longevity factor Sir2α deacetylase, indicating that PARP induction and subsequent depletion of NAD levels are the sequence of events causing angiotensin II-mediated cardiomyocyte cell death. In conclusion, these results demonstrate that PARP is a nuclear integrator of angiotensin II-mediated cell signaling contributing to cardiac hypertrophy and suggest that this could be a novel therapeutic target for the management of heart failure.

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