Angiotensin-Converting Enzyme Inhibition Attenuates Hypofibrinolysis and Reduces Cardiac Perivascular Fibrosis in Genetically Obese Diabetic Mice

Zaman, A.K.M. Tarikuz; Fujii, Satoshi; Sawa, H.; Goto, Daisuke; Ishimori, Naoki; Watano, Keiko; Kaneko, Takeaki; Furumoto, Tomoo; Sugawara, Taeko; Sakuma, Ichiro; Kitabatake, Akira; Sobel, Burton E.

doi:10.1161/01.cir.103.25.3123

Cited by 69 publications

(41 citation statements)

References 35 publications

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“…Altered characteristics of left ventricular capillaries in genetically obese diabetic rats have been reported (47). In a preliminary study, we also characterized capillary profiles in fructose-fed rats.…”

Section: Discussionmentioning

confidence: 89%

Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats

Shen

Tan

et al. 2008

Mol Med

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Metabolic syndrome is associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathy, and elevated inflammatory status. To determine whether metabolic syndrome-associated elevation of the inflammatory cytokine interleukin-18 (IL-18) in serum and cardiac tissue, and its potential sequelae could be attenuated pharmacologically, we studied fructose-fed rats. The fructose-fed rats exhibited increases in systolic blood pressure (SBP), body weight, heart weight, left ventricular weight, and blood insulin. Serum IL-18 levels in these rats were also elevated significantly. These changes were significantly different compared to those in control rats. Perivascular fibrosis around coronary arterioles was evident in the fructose-fed rats, accompanied by a paralleled increase in IL-18 by immunohistochemical analysis and real time polymerase chain reaction. Felodipine attenuated the increased levels in serum IL-18 and cardiac IL-18 mRNA as well as coronary perivascular fibrosis. Thus, augmented IL-18 in serum and cardiac tissue in metabolic syndrome may contribute to the coronary perivascular fibrosis; felodipine administration can attenuate the inflammatory and fibrosis process.

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Section: Discussionmentioning

confidence: 89%

Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats

Shen

Tan

et al. 2008

Mol Med

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“…30,31 An angiotensin-converting enzyme inhibitor decreased the inflammatory response in the myocardium of diabetic animals. 32 An ARB improved cardiac diastolic function and decreased fibrosis of diabetic rats. 33 In the present study, cardiac function was impaired in db/db mice, which is what was found in previous reports, 34,35 and candesartan treatment improved cardiac function.…”

Section: Discussionmentioning

confidence: 89%

Angiotensin II Receptor Antagonist Attenuates Expression of Aging Markers in Diabetic Mouse Heart

Kosugi

Shioi

Watanabe-Maeda

et al. 2006

Circ J

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“…This may point to fat storage/turnover capacity as the major process for long-term weight gain in men. In genetically obese diabetic mice, it was shown that ACE-inhibition blocks PAI-1 activity indicating that ACE is necessary for the formation of active PAI-1 (Zaman et al 2001). ACE converts angiotensin I into angiotensin II, and in humans, angiotensin II increases the expression of PAI-1, whereas inhibition of ACE decreases PAI-1 in plasma and tissues (Brown et al 1998(Brown et al , 1999.…”

Section: Discussionmentioning

confidence: 99%

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

et al. 2014

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Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % ([8 kg/ 10 year; n = 237). Starting BMI was between 20 and 35 kg/m 2 and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (v 2 p = 0.005), ACE rs4340 (v 2 p = 0.006) and AKR1C2 rs12249281 (v 2 p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (v 2 p = 0.00001). The A-allele of FTO was associated with a 1.999 higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.509 higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.

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Angiotensin-Converting Enzyme Inhibition Attenuates Hypofibrinolysis and Reduces Cardiac Perivascular Fibrosis in Genetically Obese Diabetic Mice

Abstract: Thus, inhibition of proteo(fibrino)lysis and augmented tissue factor expression in the heart precede and may contribute to the coronary perivascular fibrosis seen with obesity and insulin resistance. Furthermore, inhibition of ACE activity can attenuate all 3 phenomena.

Cited by 69 publications

References 35 publications

Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats

Felodipine Reduces Cardiac Expression of IL-18 and Perivascular Fibrosis in Fructose-Fed Rats

Angiotensin II Receptor Antagonist Attenuates Expression of Aging Markers in Diabetic Mouse Heart

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

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