Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients

Hirayama, Hiroyoshi; Shinoda, Masahiro; Abe, Nobuyuki; Yonemoch, Hidetoshi; Makino, Naoki

doi:10.1016/s0167-5273(00)00411-3

Cited by 32 publications

(15 citation statements)

References 20 publications

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“…Several lines of evidence suggest that PPAR-g agonists have beneficial effects in patients with cardiovascular disease. [25][26][27] The PROactive study, a large-scale randomized clinical trial, demonstrated that Pioglitazone, a full PPAR-g agonist, reduces the occurrence of all-cause mortality, non-fatal MI, and stroke in diabetic patients. 28 Previous experimental investigations revealed that PPAR-g agonists can improve LV systolic and diastolic function by attenuating unfavorable LV remodeling in animal models of MI.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

Maejima

Okada

Haraguchi

et al. 2011

Laboratory Investigation

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Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) leads to cardiac dysfunction. We examined whether Telmisartan, an angiotensin (Ang) II type I receptor blocker (ARB), could improve the recovery of LV function in a rat model of MI. The effect of Telmisartan as a peroxisome proliferator-activated receptor-g (PPAR-g) agonist was also investigated. After 28 days of MI, a significant improvement of survival was observed in the Telmisartan-treated rat group compared with the vehicle control rat group, non-PPAR-g agonistic ARB (Losartan)-treated rat group, and Telmisartan plus specific PPAR-g antagonist (GW9662)-treated rat group. Although no significant differences of blood pressure or infarct size were observed among these four groups, the Telmisartan group had better systolic and diastolic LV function. There was a significant reduction of the plasma brain natriuretic peptide level, cardiac fibrosis area, infiltration of macrophages, size of cardiomyocytes, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive myocytes, activation of matrix metalloproteinases-2 and -9 (MMPs-2/9), and expression of transforming growth factor b-1 (TGF-b1), connective tissue growth factor (CTGF), and osteopontin (OPN), while expression of PPAR-g and activation of tissue inhibitor of metalloproteinase-1 (TIMP-1) was enhanced, in the noninfarcted myocardium of rats from the Telmisartan group compared with the other three groups. To mimic ischemic conditions in vitro, neonatal rat cardiomyocytes and cardiac fibroblasts were incubated in hypoxic condition for 24 h. Increased transcriptional activation of PPAR-g and TIMP-1, and inhibition of TGF-b1 expression were observed in cardiomyocytes, while decreased activation of MMPs-2/9 and decrease in CTGF and OPN expression was seen in cardiac fibroblasts cultured with Telmisartan. In conclusion, Telmisartan prevented unfavorable cardiac remodeling through a reduction of cardiac hypertrophy and fibrosis. An anti-inflammatory effect and PPAR-g activation were suggested to be important in addition to suppression of Ang II activity. Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) is characterized by hypertrophy associated with interstitial fibrosis of the noninfarcted myocardium, and causes LV dilatation and cardiac dysfunction. It is known that angiotensin II (Ang II) has a crucial role in the development of unfavorable LV remodeling, and recent studies based on animal experiments have demonstrated that treatment with an Ang-converting enzyme inhibitor (ACE-I) and/or Ang II type I receptor blocker (ARB) can attenuate unfavorable LV remodeling. 1,2 Moreover, other experimental studies suggested that activation of peroxisome proliferator-activated receptor-g (PPAR-g), a transcription factor, improves unfavorable LV remodeling after MI. [3][4][5] PPAR-g agonists not only regulate insulin sensitivity, but also have an anti-inflammatory effect by inhibiting the expression of adhesion molecules, cytokines, and chemokines, as well ...

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Section: Discussionmentioning

confidence: 99%

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

Maejima

Okada

Haraguchi

et al. 2011

Laboratory Investigation

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“…In vivo, TZD could increase LV systolic and diastolic function in normal rats [8]. In clinical studies, it was reported that chronic treatment with troglitazone for 6 months could improve diastolic function in normotensive diabetic patients [14] and hypertensive patients [15]. Moreover, a single dose of troglitazone could increase stroke volume, LV ejection fraction and E/A ratio in diabetic patients with congestive heart failure [16].…”

Section: Pparγ Ligand and Cardiac Functionmentioning

confidence: 99%

Effect of peroxisome proliferator-activated receptor γ ligand. Rosiglitazone on left ventricular remodeling in rats with myocardial infarction

Geng¹,

Wei²,

Jin³

et al. 2006

International Journal of Cardiology

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“…Similarly, in patients with no overt heart disease, six months of thiazolidinedione therapy has been observed to improve left ventricular diastolic function. 48,49 In these latter studies, however, no additional mechanism was addressed that could explain these effects. Given the known cardiovascular risk of insulin resistance and its associated cardiometabolic abnormalities including oxidative stress, their improvement by TZD therapy appears particularly promising for preventing diabetic cardiomyopathy in the early stage of diabetic disease and should be evaluated accordingly.…”

Section: Cardiac Function and Thiazolidinedionesmentioning

confidence: 99%

Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease

Bibra

Diamant

Scheffer

et al. 2008

Diabetes and Vascular Disease Research

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T he effects of thiazolidinediones on cardiac function are controversial in humans with type 2 diabetes (T2DM) and in animals. Given the high prevalence and prognostic relevance of diastolic myocardial dysfunction in T2DM, we tested the hypothesis that by reducing oxidative stress rosiglitazone, but not glimepiride, may improve diastolic function.This randomised cross-over study investigated 12 metformin-treated T2DM patients without cardiovascular disease before and after 16 weeks of additional therapy with rosiglitazone (8 mg daily) or glimepiride (3 mg daily). Systolic and diastolic myocardial velocity (E') were assessed with tissue Doppler.In spite of similar non-significant lowering of glycosylated haemoglobin (HbA 1C ), rosiglitazone, but not glimepiride, significantly improved E' (p=0.04), reduced malondialdehyde (p=0.028), lowered high-sensitivity C-reactive protein (hsCRP) (p=0.019), and increased adiponectin (p=0.002). For rosiglitazone, multivariate regression analysis revealed malondialdehyde reduction as an independent determinant of treatment-induced improvement in E'.The rosiglitazone-induced improvements of diastolic function and oxidative stress may be of prognostic relevance in choosing therapy for T2DM patients without overt heart disease. 2008;5:310-18 doi:10.3132/dvdr.2008.045 Key words: diastolic function, oxidative stress, rosiglitazone, thiazolidinediones, tissue Doppler, type 2 diabetes. Diabetes Vasc Dis Res IntroductionThe effect of thiazolidinediones (TZDs) on cardiac function in patients with type 2 diabetes mellitus (T2DM) is under debate. Thiazolidinediones improve diabetic cardiomyopathy in animal models, 1-3 whereas their use in humans has been associated with fluid retention and congestive heart failure. [4][5][6][7][8] Among the first manifestations of cardiac abnormalities in diabetic patients are impairments of diastolic function, endothelial function and coronary flow reserve; all of these are not assessed routinely in clinical practice, but may improve if treated appropriately. [9][10][11][12][13] Interestingly, these myocardial abnormalities are found not only in patients with established diabetes but also in those with impaired glucose tolerance and insulin resistance.14,15 Indeed, insulin resistance is regarded as a cardiovascular risk factor long before the onset of overt T2DM. 16,17 Most of the mechanisms involved relate to metabolic abnormalities, endothelial dysfunction, oxidative stress and release of inflammatory cytokines. [17][18][19][20] In animals, thiazolidinediones have been shown to improve cardiac contractile function directly or indirectly by enhancing insulin sensitivity and reducing inflammation and oxidative stress. [1][2][3]19 The action of thiazolidinediones on diastolic myocardial function in relation to these factors has not yet been demonstrated in man, however.Given the high occurrence of diastolic myocardial dysfunction in patients with T2DM and its prognostic relevance, [20][21][22] we tested the hypothesis that the thiazolidinedione...

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Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients

Cited by 32 publications

References 20 publications

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

Effect of peroxisome proliferator-activated receptor γ ligand. Rosiglitazone on left ventricular remodeling in rats with myocardial infarction

Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease

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