Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease

Forst, Thomas; Karagiannis, E.; Lübben, G.; Hohberg, C.; Schöndorf, Thomas; Dikta, Gerhard; Drexler, Mark; Morcos, Michael; Dänschel, Wilfried; Borchert, Margret; Pfützner, Andreas

doi:10.1016/j.atherosclerosis.2007.05.006

Cited by 33 publications

(26 citation statements)

References 47 publications

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“…1 3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA) reductase inhibitors like atorvastatin, as well as TZDs like pioglitazone, have been shown to reduce IMT of the common carotid artery and to improve several cardiovascular risk markers in diabetic and non-diabetic patients. 8,9,[12][13][14][20][21][22] Since both drugs have different modes of action, it seems possible that the combination of statins with TZDs might provide additive clinical benefit in patients at cardiovascular risk. In accordance with previous studies, recent investigations have confirmed a reduction in IMT and an improvement in arterial elasticity during atorvastatin treatment in patients with CVD.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk

Forst

Wilhelm

Pfützner

et al. 2008

Diabetes and Vascular Disease Research

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Key words: atherosclerosis, inflammation, intima-media thickness, PPARγ, statins. IntroductionAtherosclerosis is a complex process that progresses through various functional and morphological alterations in the vessel wall, cumulating in overt cardiovascular disease. Measurement of the intima-media thickness (IMT) of the common carotid artery (CCA) by ultrasound has been established as a reliable screening tool for atherosclerosis and has been shown to predict the risk for stroke and ischaemic heart disease.1 Further, increased arterial stiffness measured by applanation tonometry is predictive for stroke, myocardial infarction and other macrovascular complications.2 In addition to these vascular measurements, laboratory markers of lipid metabolism, inflammation, adhesion molecules and new laboratory markers characterise the metabolic syndrome. Recently, intact proinsulin and adiponectin have been established as criteria of the metabolic syndrome and as predictors of cardiovascular risk in this high-risk population. 3,4The most common intervention to contain the atherosclerotic process and to reduce cardiovascular risk is treatment with 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, or statins. 5,6 Besides lowering of plasma lipids, treatment with statins has been shown to exert several pleiotropic effects, including a reduction in IMT and an improvement in arterial elasticity. 7,8 During recent years, increasing attention has been paid to the role of insulin resistance and the metabolic syndrome in the development of atherosclerosis and cardiovascular disease. Peroxisome proliferator-activated receptor (PPAR)γ agonists (thiazolidinediones), such as pioglitazone, are a class In a recent study, pioglitazone in addition to simvastatin treatment was shown to improve insulin resistance, to inhibit low-grade inflammation and to improve the overall cardiovascular risk profile even in non-diabetic patients with cardiovascular disease (CVD). 15,16 The aim of this study was to evaluate the effect of pioglitazone in addition to atorvastatin compared to atorvastatin alone on intimamedia thickness, vascular elasticity and several cardiovascular risk markers in a non-diabetic patient population at cardiovascular risk. MethodsThis study was a two-centre, prospective, double-blind, placebo-controlled trial, evaluating the effects of pioglitazone in addition to atorvastatin on IMT, arterial stiffness, endothelial function and several laboratory markers predictive for cardiovascular risk. The study was performed according to the Declaration of Helsinki and Good Clinical Practice, it was approved by the local ethical review board and all patients gave their written informed consent prior to study entry.Patients and study procedure Non-diabetic patients at increased cardiovascular risk, defined as those with an IMT greater than 0.8 mm and a previous medical history of myocardial infarction, coronary angiography with proven CVD, unstable angina pectoris, cervical or leg vessels with atherosclerotic alterations demon...

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Section: Discussionmentioning

confidence: 99%

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk

Forst

Wilhelm

Pfützner

et al. 2008

Diabetes and Vascular Disease Research

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“…Rosiglitazone, a thiazolidinedione, reduces circulating levels of MMP-9, IL-6, white blood cells and other inflammatory markers in type 2 diabetes [257,258], subsequently reducing neointimal hyperplasia [259]. Moreover, gliclazide reduces oxidized LDL-mediated MMP-9 expression in human aortic ECs in vitro [168] and pioglitazone, compared with placebo, significantly decreases plasma MMP-9 levels in diabetic patients with coronary artery disease [260]. Thiazolidinediones may also influence MMP-1 expression in vascular ECs [261].…”

Section: Inhibition Of Metalloproteinases As Therapeutic Strategies Fmentioning

confidence: 99%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…Indeed, studies have demonstrated that pioglitazone therapy benefits individuals with elevated hs-CRP values. [46][47][48][49][50][51][52][53] 54 published data of 136 Japanese type 2 diabetes patients showing that pioglitazone treatment (30 mg daily for 3 months) significantly reduced hyperglycemia and hs-CRP relative to an untreated control group. In fact, a stratification into glycemic control responders [>1% of reduction in hemoglobin A1c (HbA1c)] and nonresponders revealed that CRP reduction with pioglitazone occurred independently of changes in parameters related to glucose metabolism.…”

Section: Effects Of Pioglitazone Treatment On Hs-crp Reductionmentioning

confidence: 99%

“…We concluded that even before effects on glucose metabolism could be obtained, pioglitazone exerted immediate effects on plasma markers of inflammation. 48 The PioSwitch study converted 98 type 2 diabetes patients with residual β-cell function from insulin therapy to treatment with pioglitazone and glimepiride for 6 months. For the majority of patients, the switch from insulin therapy was possible without deterioration of blood glucose control and resulted in a significant decrease of hs-CRP levels (p < 0.01 vs baseline).…”

Section: Effects Of Pioglitazone Treatment On Hs-crp Reductionmentioning

confidence: 99%

High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone

Pfützner

Schöndorf

Hanefeld

et al. 2010

J Diabetes Sci Technol

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Abbreviations: (BMI) body mass index, (CVD) cardiovascular disease, (HbA1c) hemoglobin A1c, (HOMA) homeostasis model assessment, (hs-CRP) high-sensitivity C-reactive protein, (LDL) low-density lipoprotein, (PPARγ) peroxisome proliferator-activated receptor-γ Keywords: atherosclerosis, diabetes, hs-CRP, inflammation, insulin resistance, pioglitazone AbstractSystemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals. Data suggest that hs-CRP may also participate directly in the process of atherogenesis. A growing number of clinical trials tested the hypothesis that antidiabetic drugs specifically targeting insulin resistance could benefit individuals by reducing inflammation, atherogenesis, and thus cardiovascular risk. One such class are the thiazolidinediones (pioglitazone and rosiglitazone). These agents act as selective ligands of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). This article reviewed published data on hs-CRP changes with the thiazolidinedione agent pioglitazone. Here we found pronounced insulin-sensitizing and anti-inflammatory properties in different clinical settings, including diabetic and nondiabetic individuals. Coadministration of pioglitazone to antilipidemic statin therapy resulted in additional effects on low-grade inflammation, and hs-CRP reduction has been demonstrated to occur independently of glucose lowering. The anti-inflammatory effect appeared to be a rapid physiologic reaction on PPARγ activation and could be observed within a short-term interval after starting pioglitazone therapy. In summary, clinical study results underline the benefit of an early insulin resistance treatment to oppose systemic vascular inflammation and cardiometabolic syndrome in patients with elevated levels of high-sensitivity C-reactive protein.

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Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease

Cited by 33 publications

References 47 publications

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone

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