remodeling in obese-insulin-resistant rats. However, vildagliptin reduced cardiac hypertrophy better than other regimens in this model. In ND-fed rats, both vildagliptin and enalapril exerted cardioprotection against adverse LV remodeling. However, metformin
Nattayaporn Apaijai, Tharnwimol Inthachai, Suree Lekawanvijit, Siriporn C Chattipakorn and Nipon Chattipakorn
Victor P Bilan, Eman M Salah, Sheldon Bastacky, Huw B Jones, Rachel M Mayers, Bradley Zinker, Simon M Poucher and Stevan P Tofovic
cardiac hypertrophy (35% increase in heart weight). Notably, direct hypertrophic effects of rosiglitazone through interaction with growth-promoting signaling pathways have been suggested ( Bell & McDermott 2005 , Festuccia et al . 2009 ). Long
H Kobori, A Ichihara, Y Miyashita, M Hayashi and T Saruta
It is well known that renal hypertrophy is induced by hyperthyroidism; however, the mechanism is not fully understood. We recently reported that cardiac hypertrophy in hyperthyroidism is mediated by enhanced cardiac expression of renin mRNA. The present study addresses the hypothesis that renal hypertrophy in hyperthyroidism is mediated by amplification of renal expression of renin mRNA. Twenty Sprague-Dawley rats were divided into control (n=5) and hyperthyroid groups by daily intraperitoneal injections of saline vehicle or thyroxine. The hyperthyroid group was subdivided further into hyperthyroid-vehicle (n=5), hyperthyroid-losartan (n=5), and hyperthyroid-nicardipine (n=5) groups by daily intraperitoneal injections of saline vehicle, losartan, or nicardipine. All rats were killed at 4 weeks, and the blood and kidneys were collected. The kidney-to-body weight ratio increased in the hyperthyroid groups (+34%). Radioimmunoassays and reverse transcriptase-polymerase chain reaction revealed increased renal renin (+91%) and angiotensin II (+65%) levels and enhanced renal renin mRNA expression (+113%) in the hyperthyroid groups. Losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced renal hypertrophy. These results suggest that thyroid hormone activates the intrarenal renin-angiotensin system via enhancement of renal renin mRNA expression, which then leads to renal hypertrophy.
K De, G Ghosh, M Datta, A Konar, J Bandyopadhyay, D Bandyopadhyay, S Bhattacharya and A Bandyopadhyay
Experiments were carried out to identify the altered genes in hyperthyroid rat heart and their influence on the functions of cardiac myocytes. Chronic treatment of rats with 3,5,3' triiodo-L-thyronine (T3) resulted in a prominent increase in the size of the left ventricle with increased wall thickness and reduced chamber volume leading to concentric cardiac hypertrophy. The heart weight to body weight ratio (HW/BW) in hyperthyroid rats was increased by about 58% over that of normal rats. Using cDNA microarray comprising 588 genes, we compared the differences in mRNA expression of hyperthyroid and normal rat heart. Based on a threshold of greater than 10% change, about 37 genes were found to be regulated by T3. Further analyses by Western blotting, Northern blotting and real-time quantitative RT-PCR of some of the genes confirmed the microarray results. The T3-altered genes encode various types of proteins related to metabolism, matrix and cytoskeletal structures, growth factors, transcription factors, Ca(2+)-channels etc. The physiological significance of one of these altered proteins in hyperthyroid heart, insulin-responsive glucose transporter (GLUT) type 4 (GLUT4), was studied in detail. The expression of GLUT4 was drastically reduced in the ventricular tissues of hyperthyroid heart. Insulin-induced glucose uptake in hyperthyroid cardiomyocytes was reduced significantly, indicating the impaired glucose transport in cardiac cells. Interestingly, a few genes such as GLUT4, cytochrome P450 isoforms, superoxide dismutase (SOD), collagens, matrix metalloproteinases (MMP), tissue inhibitors of matrix metalloproteinases etc. which had not been reported earlier were found to be altered in hyperthyroid heart. Our results show some new aspects of hyperthyroid heart which will be important in assessing the pathophysiology of hypertrophied cardiomyocytes.
CI Pantos, VA Malliopoulou, IS Mourouzis, EP Karamanoli, SM Tzeis, HC Carageorgiou, DD Varonos and DV Cokkinos
The present study was undertaken to investigate heat stress protein (HSP)-70 mRNA induction and p38 MAP kinase (MAPK) activity in response to ischaemic stress in the hyperthyroid rat heart. L-Thyroxine (T(4)) (25 microg/100 g body weight) was administered to Wistar rats for 2 days (THYRacute) or 14 days (THYR), while animals treated similarly with normal saline served as controls (NORMacute and NORM). In addition, abdominal aortic banding was performed in another group of rats to produce constriction-induced hypertrophy (HYP), while sham-operated (SOP) animals served as controls. Isolated rat hearts were perfused in a Langendorff mode. Hearts from NORMacute (n=6), THYRacute animals (n=8), NORM (n=6), THYR (n=6), SOP (n=5) and HYP (n=7) animals were subjected to 20 min of zero-flow global ischaemia followed by 45 min of reperfusion. HSP70 mRNA expression and phosphorylated p38 MAPK protein expression were detected in response to ischaemia and protein kinase C-epsilon (PKCepsilon) protein expression was detected at baseline. Thyroid hormones were measured in plasma. Long-term T(4) administration and aortic constriction resulted in the development of cardiac hypertrophy. Thyroid hormones were increased in both THYR and THYRacute as compared with normal groups (P<0.05). HSP70 mRNA induction was increased 2.3-fold in THYR as compared with NORM hearts (P<0.05), whereas there was not any difference between THYRacute and NORMacute hearts (P>0.05). Phosphorylated p38 MAPK protein expression was 2.2-fold more in NORM than in THYR hearts (P<0.05), but it was not different between NORMacute and THYRacute hearts (P>0.05). HSP70 mRNA induction was 1.8-fold greater in HYP than in SOP hearts (P<0.05), whereas phosphorylated p38 MAPK protein expression was similar between the two groups (P>0.05). PKCepsilon protein expression at baseline was 1.7-fold more in NORM than in THYR hearts (P<0.05), and not different between NORMacute and THYRacute hearts (P>0.05) as well as HYP and SOP hearts (P>0.05). This study shows that HSP70 mRNA expression is increased, whereas p38 MAPK activation is attenuated in response to ischaemia in long-term T(4)-treated rat hearts as compared with normal and acute hyperthyroid hearts.
Bao-Wei Wang, Hang Chang, Peiliang Kuan and Kou-Gi Shyu
, two studies reported that myostatin is an inhibitor of cardiomyocyte proliferation and reduces cardiac mass ( Atraza et al . 2007 , McKoy et al . 2007 ), while one study reported that myostatin does not regulate cardiac hypertrophy or fibrosis
Félix Vargas, Isabel Rodríguez-Gómez, Pablo Vargas-Tendero, Eugenio Jimenez and Mercedes Montiel
established hypertension have not been explained, although they may involve irreversible morphological changes in the vascular wall ( Folkow 1990 ). Cardiac mass Mechanisms underlying cardiac hypertrophy secondary to elevated thyroid hormone levels include a
Priyanka De, Sreerupa Ghose Roy, Dipak Kar and Arun Bandyopadhyay
for a prolonged duration may cause considerable changes in myocardium such as tissue remodeling, ventricular hypertrophy, and myocyte dysfunction ultimately leading to heart failure ( Maron 2002 , Xu et al . 2007 ). Initially, cardiac hypertrophy
Å Tivesten, E Bollano, H C Nyström, C Alexanderson, G Bergström and A Holmäng
function and experimental atherosclerosis in females ( Hodgin & Maeda 2002 , Mendelsohn & Karas 2005 ). Oestrogens have also been suggested to modulate cardiac mass and attenuate the development of cardiac hypertrophy in females ( van Eickels et al. 2001
M Jankowski, D Wang, S Mukaddam-Daher and J Gutkowska
cardiac hypertrophy is exaggerated, and its resolution remains incomplete after parturition ( Simmons et al. 2002 ). In response to elevated female steroid hormones during gestation, cardiac growth and contractility are modulated profoundly in