Diabetic cardiomyopathy

Asghar, Omar; Alsunni, Ahmed A; Khavandi, Kaivan; Khavandi, Ali; Withers, Sarah; Greenstein, Adam; Heagerty, AM; Malik, Rayaz A.

doi:10.1042/cs20080500

Cited by 155 publications

(151 citation statements)

References 204 publications

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“…Increased PI3K(p110α) activity prevents diabetes-induced increases in cardiomyocyte size, fibrosis and apoptosis Cardiomyocyte hypertrophy, fibrosis and apoptosis all contribute to the pathogenesis and progression of diabetic cardiomyopathy [24,25]. Induction of diabetes in Ntg mice for 12 weeks had no impact on heart weight (HW; see HW/ TL, Table 1) but was associated with increased cardiomyocyte width (≈13%; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…LV diastolic dysfunction is one of the earliest manifestations of diabetic cardiomyopathy, presenting prior to the onset of systolic dysfunction [26,31,32]. Diastolic dysfunction is characterised by abnormal LV relaxation and filling, associated with elevated LVEDP, a depressed E/A ratio and increased deceleration time [25]. Contributing factors include pathological cardiomyocyte hypertrophy, increased cell death and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes

et al. 2012

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Aims/hypothesis Diabetic cardiomyopathy is characterised by diastolic dysfunction, oxidative stress, fibrosis, apoptosis and pathological cardiomyocyte hypertrophy. Phosphoinositide 3-kinase (PI3K)(p110α) is a cardioprotective kinase, but its role in the diabetic heart is unknown. The aim of this study was to assess whether PI3K(p110α) plays a critical role in the induction of diabetic cardiomyopathy, and whether increasing PI3K(p110α) activity in the heart can prevent the development of cardiac dysfunction in a setting of diabetes.Methods Type 1 diabetes was induced with streptozotocin in adult male cardiac-specific transgenic mice with increased PI3K(p110α) activity (constitutively active PI3K [p110α], caPI3K] or decreased PI3K(p110α) activity (dominantnegative PI3K [p110α], dnPI3K) and non-transgenic (Ntg) mice for 12 weeks. Cardiac function, histological and molecular analyses were performed. Results Diabetic Ntg mice displayed diastolic dysfunction and increased cardiomyocyte size, expression of atrial and B-type natriuretic peptides (Anp, Bnp), fibrosis and apoptosis, as well as increased superoxide generation and increased protein kinase C β2 (PKCβ2), p22 phox and apoptosis signalregulating kinase 1 (Ask1) expression. Diabetic dnPI3K mice displayed an exaggerated cardiomyopathy phenotype compared with diabetic Ntg mice. In contrast, diabetic caPI3K mice were protected against diastolic dysfunction, pathological cardiomyocyte hypertrophy, fibrosis and apoptosis. Protection in diabetic caPI3K mice was associated with attenuation of left ventricular superoxide generation, attenuated Anp, Bnp, PKCβ2, Ask1 and p22 phox expression, and elevated AKT. Further, in cardiomyocyte-like cells, increased PI3K(p110α) activity suppressed high glucose-induced superoxide generation and enhanced mitochondrial function. Conclusions/interpretation These results demonstrate that reduced PI3K activity accelerates the development of diabetic cardiomyopathy, and that enhanced PI3K(p110α) activity can prevent adverse cardiac remodelling and dysfunction in a setting of diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes

et al. 2012

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“…33, 9, 559 -564 (2010) was correlated with HbA1c and insulin levels. 2,10,21 Diastolic dysfunction could be detected in 52%-60% of the patients in echocardiography even under close glycemic control. 20 It is also known that hyperinsulinemia can cause LV hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…thickness, increased arterial stiffness, and systolic dysfunction when compared with a matched control group. 10 In the early phase of DCMP, the pathologic changes can be reversible with strict metabolic control, but in the continuous process the myocardial changes become irreversible and the risk of developing heart failure increases. 8,11,12 Although it is common, diagnosis of DCMP is very difficult.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

Bildirici

Ural

Acar

et al. 2010

Clinical Cardiology

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Background: Diabetic cardiomyopathy (DCMP) is a common complication of diabetes and is associated with increased mortality. It has been suggested that a poor R-wave progression in a resting electrocardiogram (ECG) could be a sign of cardiomyopathy. Hypothesis: The aim of this study was primarily to analyze the relationship between poor R-wave progression and DCMP, and the effect of poor R-wave progression on cardiac functions in long-term follow-up. Methods: Seventy type 2 normotensive diabetics (33 female, 37 male; mean age, 52.9 ± 10.4 years) were included in the study. Poor R-wave progression in an ECG was defined as an R wave <3 mm in V1-3 derivations. The patients were randomized in 2 groups, which were those without (group I, n = 34) and those with poor R-wave progression (group II, n = 36). All patients underwent conventional and tissue Doppler echocardiography and were followed in an outpatient clinic setting for 4 years. Results: Demographic variables were similar between the 2 groups. In group II, left ventricular (LV) relaxation abnormality was more prevalent, the Tei index was higher, and in tissue Doppler mitral annulus Em velocities were significantly lower and Am velocities were higher than those with normal R-wave progression. At the end of the 4-year follow-up period, LV ejection fraction was decreased in group II, whereas LV mass index and Tei index were significantly increased. Conclusions: LV diastolic dysfunction is more frequently observed in diabetic patients with poor R-wave progression in ECG, which may be an early sign of LV dysfunction and DCMP in diabetics. IntroductionThe prevalence of diabetes is steadily increasing, and the number of diabetic people is expected to reach 300 million globally by 2025. 1 Cardiovascular disease is a serious of complication of diabetes and is responsible for 80% of the deaths among diabetics. 2 Although coronary artery disease is very common, heart failure is also a major cause of mortality and morbidity in patients with diabetes mellitus. 3 Up to 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. 4 The Framingham Heart Study showed that the frequency of heart failure in diabetic men is twice that of nondiabetics, and it is 5 times higher in diabetic women compared to nondiabetic women. 1,5 Diabetic cardiomyopathy (DCMP) was first reported in 1972 by Rubler. 6 It is characterized by the development of diastolic dysfunction at the early stage followed by systolic dysfunction in the absence of coronary artery disease, hypertension, or significant valvular heart disease. 7 -9 In the Strong Heart Study, diabetes was significantly related to higher left ventricular (LV) mass and wall

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“…In human diabetic myocardium, endothelial swelling and thickening of the capillary basement membrane occur (Asghar et al 2009). Human microvascular endothelial cells (HMVECs) are sensitive to IGF1s but insensitive to insulin, and IGF1Rs are several times more abundant on these cells than IRs (Chisalita & Arnqvist 2004).…”

Section: Introductionmentioning

confidence: 99%

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

Bäck

Islam

Johansson

et al. 2012

Journal of Endocrinology

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Diabetes is associated with microcirculatory dysfunction and heart failure and changes in insulin and IGF1 levels. Whether human cardiac microvascular endothelial cells (HMVEC-Cs) are sensitive to insulin and/or IGF1 is not known. We studied the role of insulin receptors (IRs) and IGF1 receptors (IGF1Rs) in metabolic, mitogenic and antiinflammatory responses to insulin and IGF1 in HMVEC-Cs and human umbilical vein endothelial cells (HUVECs). IR and IGF1R gene expression was studied using real-time RT-PCR. Receptor protein expression and phosphorylation were determined by western blot and ELISA. Metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate inflammatory responses. According to gene expression and protein in HMVEC-Cs and HUVECs, IGF1R is more abundant than IR. Immunoprecipitation with anti-IGF1R antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF1 hybrid receptors in HMVEC-Cs. IGF1 at a concentration of 10 K8 mol/l significantly stimulated phosphorylation of both IGF1R and IR in HMVEC-Cs. In HUVECs IGF1 10 K8 mol/l phosphorylated IGF1R. IGF1 stimulated DNA synthesis at 10 K8 mol/l and glucose accumulation at 10 K7 mol/l in HMVEC-Cs. TNF-a dramatically increased E-selectin expression, but no inflammatory or antiinflammatory effects of insulin, IGF1 or high glucose were seen. We conclude that HMVEC-Cs express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors. TNF-a has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.

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Diabetic cardiomyopathy

Cited by 155 publications

References 204 publications

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes

Enhanced phosphoinositide 3-kinase(p110α) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

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