Abstract 3551: Cyclophilin a Promotes Angiotensin II-Induced Inflammation and Cardiovascular Hypertrophy in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kimio Satoh ◽  
Liam Casey ◽  
Michael R O’Dell ◽  
Patrizia Nigro ◽  
Amy Mohan ◽  
...  
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Rhode Island ◽  
Bone Marrow Cells ◽  
Weight Ratio ◽  
Cyclophilin A ◽  
Ros Production ◽  
Body Weight Ratio ◽  
Cardiovascular Hypertrophy

Background - Cyclophilin A (CyPA) is a chaperone protein secreted from vascular smooth muscle cells (VSMC) in response to reactive oxygen species (ROS). We have recently demonstrated that extracellular CyPA stimulates at least 3 signaling pathways (ERK1/2, Akt and JAK) and mediates numerous cellular effects of ROS. Angiotensin II (Ang II) induces ROS through NADPH oxidases and activates matrix metalloproteinase (MMP) in VSMC. ROS and MMPs have been demonstrated to mediate cardiac hypertrophy and remodeling. We hypothesized that VSMC-derived CyPA contributes to AngII-induced cardiovascular hypertrophy in vivo due to its proinflammatory properties. Methods and Results - ApoE −/− and ApoE −/− CyPA −/− mice were treated with AngII (1000 ng/min/kg for 4 weeks) to induce cardiac hypertrophy. Long-term infusion of AngII significantly increased heart/body weight ratio in ApoE −/− mice, which was significantly less in ApoE −/− CyPA −/− mice (6.6±1.0 vs. 4.8±0.7, P <0.01). Echocar-diography confirmed a significantly greater increase in LV mass in ApoE −/− mice compared to ApoE −/− CyPA −/− mice (112% vs. 47%). Perivascular accumulation of inflammatory cells and cardiac myofibroblasts in ApoE −/− mice was significantly greater than in ApoE −/− CyPA −/− mice. Consequently, coronary artery ROS production (DHE fluorescence) and MMP activation (in situ zymography) were markedly increased by AngII in ApoE −/− mice compared to ApoE −/− CyPA −/− mice. To determine the source of CyPA, bone marrow cells (BMCs) transplantation was performed. The heart/body weight ratio was still higher in ApoE −/− mice compared with ApoE −/− CyPA −/− mice after reconstitution with GFP + CyPA +/+ BMCs (6.7±0.6 vs. 5.6±0.9, P <0.01). Recruitment of GFP + BMCs to the heart in chimeric ApoE −/− mice was significantly greater than the chimeric ApoE −/− CyPA −/− mice (count/area; 218±63 vs. 109±43, P <0.01). To prove a vascular source of CyPA was essential, VSMC-specific CyPA overexpressing mice were generated. In these mice there was a significant increase in cardiac MMP activity after AngII infusion (VSMC-Tg > WT > CyPA −/− ). Conclusion - CyPA is a novel mediator of AngII-induced cardiac hypertrophy by stimulating vascular ROS production, MMP activation, and inflammatory cell recruitment. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

2019 ◽  
Vol 116 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Hairuo Lin ◽  
Yang Li ◽  
Hailin Zhu ◽  
Qiancheng Wang ◽  
Zhenhuan Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cardiac Remodelling ◽  
Heart Weight ◽  
Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice

1994 ◽  
Vol 266 (6) ◽  
pp. H2468-H2475 ◽  
Author(s):  
H. A. Rockman ◽  
S. P. Wachhorst ◽  
L. Mao ◽  
J. Ross
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Heart Weight ◽  
Receptor Blockade ◽  
Body Weight Ratio

There is increasing evidence that the renin-angiotensin system may play a important role in cardiac hypertrophy. To assess the role of angiotensin II in the induction of cardiac hypertrophy, three groups of adult mice were subjected to left ventricular pressure overload by transverse aortic constriction (TAC). For the next 7 days the groups received either the specific angiotensin II subtype 1 receptor (AT1) antagonist (losartan, 1.05 g/l; n = 17), an angiotensin enzyme inhibitor (captopril, 2 g/l; n = 17), or no treatment (n = 22) administered in the drinking water and compared with three similarly treated sham-operated groups (n = 7 each). TAC resulted in a significant increase in heart weight-to-body weight ratio (0.634 +/- 0.087 vs. 0.525 +/- 0.039, g/g x 100, P < 0.05), which was prevented by losartan (0.506 +/- 0.069, g/g x 100, P < 0.0001) despite similar hemodynamic load (proximal systolic pressure 146 +/- 31 vs. 136 +/- 32 mmHg, untreated vs. losartan, P = NS). Proximal systolic pressure was positively correlated with the development of ventricular hypertrophy. In the presence of AT1-receptor blockade, the increase in heart weight-to-body weight ratio at any given systolic pressure was significantly attenuated compared with untreated TAC mice. The increase in heart weight-to-body weight ratio was also significantly attenuated by captopril compared with untreated banded controls (0.542 +/- 0.091, g/g x 100, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract 16205: MKP-5 Deficiency Attenuates Pressure Overload-induced Cardiac Hypertrophy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kisuk Min ◽  
Yan Huang ◽  
Frank J Giordano ◽  
Sudip Bajpeyi ◽  
Anton M Bennett
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Molecular Mechanisms ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Body Weight Ratio ◽  
Pathological Cardiac Hypertrophy

Introduction: Cardiac remodeling occurs in response to pathological stimuli including chronic pressure overload, subsequently leading to heart failure. Despite considerable research efforts, the molecular mechanisms responsible for heart failure have yet to be fully elucidated. One of the prominent signaling pathways involved in the development of pathological cardiac hypertrophy is the mitogen-activated protein kinases (MAPKs) pathways. The MAPKs are inactivated by the MAPK phosphatases (MKPs) through direct dephosphorylation. Growing evidence suggests the importance of MKP-5 signaling mechanisms in physiological and pathological processes. However, the role of MKP-5 has not been explored in cardiac muscle. The objective of this study is to investigate how MKP-5-mediated MAPK activity contributes to mechanisms responsible for pressure overload-induced cardiac hypertrophy. Hypothesis: We tested the hypothesis that MKP-5 serves as a central regulator of MAPKs in pressure overload-induced cardiac hypertrophy. Methods: To investigate the role of MKP-5 in cardiac muscle, we caused pressure overload-induced cardiac hypertrophy in wild type (mkp-5 +/+ ) mice and MKP-5 deficient mice (mkp-5 -/- ) through transverse aortic constriction (TAC). Cardiac function was evaluated by echocardiographic analysis at 4 weeks after TAC. Cardiac hypertrophy was measured by heart-to-body weight ratio. Interstitial myocardial fibrosis was evaluated by Sirius red stains and expression of fibrogenic genes was determined by quantitative PCR. Results: Echocardiographic analysis showed that the ejection fraction and fractional shortening of mkp-5 +/+ mice significantly decreased by at 4 weeks after TAC. Heart-to-body weight ratio increased in mkp-5 +/+ mice. However, MKP-5-deficient heart was protected from cardiac dysfunction and cardiac hypertrophy induced by TAC. Importantly, the fibrogenic genes were markedly reduced in mkp-5 -/- mice as compared with mkp-5 +/+ mice at 4 weeks after TAC. Conclusions: Collectively, our study demonstrates that MKP-5 deficiency prevents the heart from pressure overload-induced cardiac hypertrophy and suggests that MKP-5 may serve as a novel therapeutic target for treatment of heart disease.

Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

1999 ◽  
Vol 276 (2) ◽  
pp. H350-H358 ◽  
Author(s):  
Masaaki Koide ◽  
Blase A. Carabello ◽  
Chester C. Conrad ◽  
John M. Buckley ◽  
Gilberto DeFreyte ◽  
...  
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Weight Ratio ◽  
Renin Angiotensin System ◽  
Angiotensin Ii Receptor ◽  
Body Weight Ratio ◽  
Cardiac Growth ◽  
Angiotensin System ◽  
Hypertrophic Response ◽  
Hemodynamic Overload

Myocardial hypertrophy is one of the basic mechanisms by which the heart compensates for hemodynamic overload. The mechanisms by which hemodynamic overload is transduced by the cardiac muscle cell and translated into cardiac hypertrophy are not completely understood. Candidates include activation of the renin-angiotensin system (RAS) and angiotensin II receptor (AT1) stimulation. In this study, we tested the hypothesis that load, independent of the RAS, is sufficient to stimulate cardiac growth. Four groups of cats were studied: 14 normal controls, 20 pulmonary artery-banded (PAB) cats, 7 PAB cats in whom the AT1 was concomitantly and continuously blocked with losartan, and 8 PAB cats in whom the angiotensin-converting enzyme (ACE) was concomitantly and continuously blocked with captopril. Losartan cats had at least a one-log order increase in the ED50 of the blood pressure response to angiotensin II infusion. Right ventricular (RV) hypertrophy was assessed using the RV mass-to-body weight ratio and ventricular cardiocyte size. RV hemodynamic overload was assessed by measuring RV systolic and diastolic pressures. Neither the extent of RV pressure overload nor RV hypertrophy that resulted from PAB was affected by AT1 blockade with losartan or ACE inhibition with captopril. RV systolic pressure was increased from 21 ± 3 mmHg in normals to 68 ± 4 mmHg in PAB, 65 ± 5 mmHg in PAB plus losartan and 62 ± 3 mmHg in PAB plus captopril. RV-to-body weight ratio increased from 0.52 ± 0.04 g/kg in normals to 1.11 ± 0.06 g/kg in PAB, 1.06 ± 0.06 g/kg in PAB plus losartan and 1.06 ± 0.06 g/kg in PAB plus captopril. Thus 1) pharmacological modulation of the RAS with losartan and captopril did not change the extent of the hemodynamic overload or the hypertrophic response induced by PAB; 2) neither RAS activation nor angiotensin II receptor stimulation is an obligatory and necessary component of the signaling pathway that acts as an intermediary coupling load to the hypertrophic response; and 3) load, independent of the RAS, is capable of stimulating cardiac growth.

scholarly journals Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoying Zhang ◽  
Zhiying Zhang ◽  
Pengxiang Wang ◽  
Yiwei Han ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Cardiac Hypertrophy ◽  
Heart Function ◽  
Weight Ratio ◽  
Tibetan Medicine ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Body Weight Ratio ◽  
Cross Sectional

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.

Abstract P252: Smooth Muscle At1a Receptor Mediates Perivascular Fibrosis In Angiotensin Ii-infused Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Keisuke Okuno ◽  
Satoru Eguchi ◽  
Matthew A Sparks
Keyword(s):  
Body Weight ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Critical Role ◽  
Receptor Activation ◽  
Ang Ii ◽  
Cardiovascular Remodeling ◽  
At1a Receptor ◽  
Cardiovascular Hypertrophy

Angiotensin II (Ang II) signaling via AT1 receptor has been shown to play a critical role in the pathogenesis of hypertension, cardiovascular hypertrophy and fibrosis. We have demonstrated that ADAM17 expressed in vascular smooth muscle cells (VSMC) mediates EGF receptor activation and promotes cardiac hypertrophy and perivascular fibrosis induced by Ang II. It is conceivable that Ang II signaling in VSMCs specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis. In a recent study, deficiency of smooth muscle AT1a receptors results in diminished hypertension and protection from cardiac hypertrophy induced by Ang II. However, we have limited understanding whether smooth muscle AT1a receptors affects hypertensive fibrosis in vasculature. Thus, this study was designed to elucidate the roles of the AT1a receptor in VSMCs in cardiovascular remodeling including fibrosis during Ang II stimulation using VSMC AT1a receptor deficient mice. To delete the AT1a receptor from VSMCs, we crossed C57BL/6 transgenic mouse lines expressing Cre recombinase under the control of the sm22α promoter (KIsm22α-Cre). Male AT1a flox/flox KIsm22α-Cre+/- (SMKO) and Controls (AT1a flox/flox KIsm22α-Cre-/-) mice were infused with Ang II (1 μg/kg/min) for 2 weeks via osmotic mini-pump. In Control mice, Ang II infusion for 2 weeks induced cardiac hypertrophy indicated by heart-to-body weight ratio and echocardiogram. After 2 weeks of Ang II infusion, heart-to-body weight ratios were significantly increased in Control mice compared with AT1a SMKO mice (6.04 versus 4.89, respectively, p=0.032). Cardiac wall hypertrophy was seen in Controls after 2 weeks of Ang II infusion, which was attenuated in AT1a SMKOs. Control mice (n=5) showed vascular medial hypertrophy and perivascular fibrosis, whereas these phenotypic changes were attenuated in SMKO mice (n=4). In conclusion, AT1a receptors from VSMC could mediate Ang II-induced cardiovascular hypertrophy and perivascular fibrosis. Whether the data can be fully explained by the prevention of hypertension remains to be determined, the data contrast to the past manuscript showing a protective effect in AT1a flox/flox S100A4-Cre+/- mice (fibroblast silencing) with Ang II infusion.

Abstract 1428: Cyclophilin a Promotes Vascular Oxidative Stress and Accelerates Development of Angiotensin II-Induced Aortic Aneurysms

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kimio Satoh ◽  
Patrizia Nigro ◽  
Tetsuya Matoba ◽  
Michael R O’Dell ◽  
Zhaoqiang Cui ◽  
...  
Keyword(s):  
Cell Migration ◽  
Angiotensin Ii ◽  
Rhode Island ◽  
Inflammatory Cell ◽  
Aortic Wall ◽  
Bone Marrow Cells ◽  
Aortic Rupture ◽  
Gelatin Zymography ◽  
Cyclophilin A ◽  
Aortic Aneurysms

Cyclophilin A (CyPA) is a chaperone protein secreted from vascular smooth muscle cells (VSMC) in response to reactive oxygen species (ROS), that stimulates VSMC migration and inflammatory cell migration in vitro. Abdominal aortic aneurysm (AAA) formation involves inflammatory cytokine release, leukocyte recruitment, aortic wall degradation, and neovascularization. We hypothesized that VSMC-derived CyPA contributes to AAA pathogenesis due to its proinflammatory properties. To determine the role of CyPA in AAA formation, ApoE −/− and ApoE −/− CyPA −/− mice were infused with angiotensin II (AngII, 1000 ng/min/kg) for 4 weeks. There were no differences in blood pressure and cholesterol between ApoE −/− and ApoE −/− CyPA −/− mice before and after Ang II treatment. AngII-induced AAA formation and aortic rupture was frequently observed in ApoE −/− mice (89% and 40%). In contrast, ApoE −/− CyPA −/− mice were completely protected from AngII-induced AAA formation and aortic rupture (0% and 0%). ApoE −/− CyPA −/− mice showed decreased levels of monocyte chemoattractant protein (MCP)-1 in the aorta and lacked elastic lamina degradation, microvessel formation, and aortic expansion. In response to AngII, recruitment of leukocytes to the aortic wall was markedly impaired in ApoE −/− CyPA −/− mice compared with ApoE −/− mice (counts/area; 8.6±4.3 vs. 60.0±13.8, P <0.01). The incidence of AAA was 63% in CyPA +/+ marrow-transplanted ApoE −/− mice, while the incidence of AAA in ApoE −/− CyPA −/− mice remained 0% after transplantation of CyPA +/+ bone marrow cells. In situ and gelatin zymography demonstrated that CyPA was required for matrix metalloproteinase (MMP) activation in aortic wall. Treatment of mouse aortic wild-type VSMC with AngII augmented MMP activity, which was significantly less in CyPA −/− VSMC. Treatment of VSMC with 100 nM CyPA augmented MMP activity, suggesting the importance of extracellular CyPA as well as intracellular CyPA. Finally, VSMC-specific CyPA overexpressing mice revealed augmented AngII-induced MMP activity in the vascular wall. Vascular-derived CyPA contributes to AAA pathogenesis in mice by increasing proinflammatory cytokine expression, inflammatory cell migration, and MMP activation. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Age-associated increase in rat ventricular ANP gene expression correlates with cardiac hypertrophy

1995 ◽  
Vol 269 (3) ◽  
pp. H1003-H1008 ◽  
Author(s):  
A. Younes ◽  
M. O. Boluyt ◽  
L. O'Neill ◽  
A. L. Meredith ◽  
M. T. Crow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Left Atrial ◽  
Northern Blot Analysis ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Old Rats

Atrial natriuretic peptide (ANP), a cardiac-specific hormone, is stored in the atria and released in response to atrial stretch. During cardiac hypertrophy, ANP gene expression is markedly upregulated in the left ventricle (LV). Because the hearts of normotensive senescent rats exhibit left atrial (LA) and left ventricular (LV) hypertrophy and dilatation, we examined ANP mRNA levels by Northern blot analysis and ANP peptide concentrations by radioimmunoassay in atria, LVs, and plasma of rats at 2, 6, 18, and 22-24 mo of age. Compared with LVs of 6-mo-old rats, the LV-to-body weight ratio was elevated 30% by 18 mo of age, whereas levels of ANP mRNA were elevated twofold (not significant) and sevenfold (P < 0.05) in the LV of 18- and 22- to 24-mo-old rats, respectively. The concentration of immunoreactive ANP (ir-ANP) exhibited a four- to fivefold increase in LVs of 18- and 22- to 24-mo-old rats compared with values for 6-mo-old rats (43 +/- 4 pmol/g wet wt; means +/- SE). Among 18-and 22- to 24-mo-old rats a significant correlation was observed between ANP peptide concentration and LV hypertrophy (r 2 = 0.64). Levels of ANP mRNA and ir-ANP in the atria exhibited only modest changes with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac remodeling caused by transgenic overexpression of a corn Rac gene

2011 ◽  
Vol 301 (3) ◽  
pp. H868-H880 ◽  
Author(s):  
Mohammad T. Elnakish ◽  
Mohamed M. Awad ◽  
Mohamed D. H. Hassona ◽  
Mazin A. Alhaj ◽  
Aditi Kulkarni ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Systolic Dysfunction ◽  
Weight Ratio ◽  
Gtpase Activity ◽  
Body Weight Ratio ◽  
Rac Gtpase ◽  
Lv Mass

Rac1-GTPase activation plays a key role in the development and progression of cardiac remodeling. Therefore, we engineered a transgenic mouse model by overexpressing cDNA of a constitutively active form of Zea maize Rac gene (ZmRacD) specifically in the hearts of FVB/N mice. Echocardiography and MRI analyses showed cardiac hypertrophy in old transgenic mice, as evidenced by increased left ventricular (LV) mass and LV mass-to-body weight ratio, which are associated with relative ventricular chamber dilation and systolic dysfunction. LV hypertrophy in the hearts of old transgenic mice was further confirmed by an increased heart weight-to-body weight ratio and histopathology analysis. The cardiac remodeling in old transgenic mice was coupled with increased myocardial Rac-GTPase activity (372%) and ROS production (462%). There were also increases in α1-integrin (224%) and β1-integrin (240%) expression. This led to the activation of hypertrophic signaling pathways, e.g., ERK1/2 (295%) and JNK (223%). Pravastatin treatment led to inhibition of Rac-GTPase activity and integrin signaling. Interestingly, activation of ZmRacD expression with thyroxin led to cardiac dilation and systolic dysfunction in adult transgenic mice within 2 wk. In conclusion, this is the first study to show the conservation of Rho/Rac proteins between plant and animal kingdoms in vivo. Additionally, ZmRacD is a novel transgenic model that gradually develops a cardiac phenotype with aging. Furthermore, the shift from cardiac hypertrophy to dilated hearts via thyroxin treatment will provide us with an excellent system to study the temporal changes in cardiac signaling from adaptive to maladaptive hypertrophy and heart failure.

Biochemical and Pathological Aspects of Groundnut Poisoning in Chickens

1966 ◽  
Vol 3 (6) ◽  
pp. 601-615 ◽  
Author(s):  
R. B. A. Carnaghan ◽  
G. Lewis ◽  
D. S. P. Patterson ◽  
R. Allcroft
Keyword(s):  
Body Weight ◽  
Vitamin A ◽  
Rhode Island ◽  
Weight Ratio ◽  
Pathological Changes ◽  
Body Weight Ratio ◽  
Hepatic Fat ◽  
Groundnut Meal ◽  
Biochemical Features

Rhode Island Red chicks were fed from hatching to 8 weeks of age a commercial ration to which was added a highly toxic groundnut meal; groups were killed at regular intervals for biochemical and histological examinations. Growth was severely retarded and the liver/body weight ratio was increased compared with control chicks. Increased hepatic fat, reduced vitamin A storage and fluctuation in the RNA/DNA ratio were also observed. These biochemical features of groundnut toxicity are discussed in relation to pathological changes.

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