Impaired Elastic Properties of the Aorta in Fat-Fed, Streptozotocin-Treated Rats

Rationale Accelerated arterial stiffening is a major complication of diabetes with no specific therapy available up to date. Objective The present study investigates the role of the osteogenic transcription factor Runx2 as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes. Methods and Results Using a murine model of type 2 diabetes (db/db mice) we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae as well as in thoracic aortic samples from type 2 diabetic patients. Vascular smooth muscle-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that Runx2 expression in diabetes is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. Conclusion In conclusion this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes, promoting arterial stiffness irrespective of calcification.

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“…This observation is consistent with enhanced aortic collagen deposition found in other models of diabetes 24-26 .…”

Section: Discussionsupporting

confidence: 91%

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

Raaz

Schellinger

Chernogubova

et al. 2015

Circulation Research

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“…However, it should be noticed that our sample is older than Swedish healthy siblings. Evidence on this regard suggest that: 1) in diabetic rats, elastic properties of the aorta are impaired, being closely related to hyperglycemia-induced vascular wall remodelling [38], 2) in a substudy of the Finnish population-based Health 2000 Survey, FPG levels were independently associated with increased arterial stiffness [39], 3) over a 3-year period in 2080 Japanese men BP and FPG levels even below those defining hypertension and diabetes mellitus, respectively, could synergistically lead to progression of arterial stiffening [40]. …”

Section: Discussionmentioning

confidence: 99%

Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer

Matteucci

Consani

Masoni

et al. 2010

Cardiovasc Diabetol

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BackgroundNormotensive non-diabetic relatives of type 1 diabetes (T1D) patients have an abnormal blood pressure response to exercise testing that is associated with indices of metabolic syndrome and increased oxidative stress. The primary aim of this study was to investigate the circadian variability of blood pressure and the ambulatory arterial stiffness index (AASI) in healthy siblings of T1D patients vs healthy control subjects who had no first-degree relative with T1D. Secondary aims of the study were to explore the influence of both cardiovascular autonomic function and erythrocyte electron transfer activity as oxidative marker on the ambulatory blood pressure profile.MethodsTwenty-four hour ambulatory blood pressure monitoring (ABPM) was undertaken in 25 controls, 20 T1D patients and 20 siblings. In addition to laboratory examination (including homeostasis model assessment of insulin sensitivity) and clinical testing of autonomic function, we measured the rate of oxidant-induced erythrocyte electron transfer to extracellular ferricyanide (RBC vfcy).ResultsSystolic blood pressure (SBP) midline-estimating statistic of rhythm and pulse pressure were higher in T1D patients and correlated positively with diabetes duration and RBC vfcy; autonomic dysfunction was associated with diastolic BP ecphasia and increased AASI. Siblings had higher BMI, lower insulin sensitivity, larger SBP amplitude, and higher AASI than controls. Daytime SBP was positively, independently associated with BMI and RBC vfcy. Among non-diabetic people, there was a significant correlation between AASI and fasting plasma glucose.ConclusionsSiblings of T1D patients exhibited a cluster of sub-clinical metabolic abnormalities associated with consensual perturbations in BP variability. Moreover, our findings support, in a clinical setting, the proposed role of transplasma membrane electron transport systems in vascular pathobiology.

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“…Control group rats were fed a standard chow diet consisting of a total of 14 KJ/g and 8% fat. Details of the type 2 diabetic rat model process were published in our previous study (10). Fasting blood glucose (FBG) was measured by glucose oxidase method in an automatic biochemical analyzer (DVI 1650), and fasting insulin (FINS) was measured with a radioimmunoassay (RIA) kit (BNIBT Co, China) in a RIA counter (XH-6010).…”

Section: Animal Proceduresmentioning

confidence: 99%

Diastolic function of the right ventricle is impaired in experimental type 2 diabetic rat models

Miao¹,

Zhang²,

Yuan³

et al. 2014

Turk J Med Sci

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Impaired Elastic Properties of the Aorta in Fat-Fed, Streptozotocin-Treated Rats

Cited by 22 publications

References 65 publications

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer

Diastolic function of the right ventricle is impaired in experimental type 2 diabetic rat models

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