scholarly journals Dynamic micro- and macrovascular remodeling in coronary circulation of obese Ossabaw pigs with metabolic syndrome

2012 ◽  
Vol 113 (7) ◽  
pp. 1128-1140 ◽  
Author(s):  
Aaron J. Trask ◽  
Paige S. Katz ◽  
Amy P. Kelly ◽  
Maarten L. Galantowicz ◽  
Mary J. Cismowski ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Coronary Artery ◽  
Coronary Flow ◽  
Structural Changes ◽  
Velocity Ratio ◽  
Stiffness Index ◽  
Capillary Rarefaction ◽  
Glycation End Products ◽  
Pressure Myograph

Previous studies from our laboratory showed that coronary arterioles from type 2 diabetic mice undergo inward hypertrophic remodeling and reduced stiffness. The aim of the current study was to determine if coronary resistance microvessels (CRMs) in Ossabaw swine with metabolic syndrome (MetS) undergo remodeling distinct from coronary conduit arteries. Male Ossabaw swine were fed normal ( n = 7, Lean) or hypercaloric high-fat ( n = 7, MetS) diets for 6 mo, and then CRMs were isolated and mounted on a pressure myograph. CRMs isolated from MetS swine exhibited decreased luminal diameters (126 ± 5 and 105 ± 9 μm in Lean and MetS, respectively, P < 0.05) with thicker walls (18 ± 3 and 31 ± 3 μm in Lean and MetS, respectively, P < 0.05), which doubled the wall-to-lumen ratio (14 ± 2 and 30 ± 2 in Lean and MetS, respectively, P < 0.01). Incremental modulus of elasticity (IME) and beta stiffness index (BSI) were reduced in CRMs isolated from MetS pigs (IME: 3.6 × 106 ± 0.7 × 106 and 1.1 × 106 ± 0.2 × 106 dyn/cm2 in Lean and MetS, respectively, P < 0.001; BSI: 10.3 ± 0.4 and 7.3 ± 1.8 in Lean and MetS, respectively, P < 0.001). BSI in the left anterior descending coronary artery was augmented in pigs with MetS. Structural changes were associated with capillary rarefaction, decreased hyperemic-to-basal coronary flow velocity ratio, and augmented myogenic tone. MetS CRMs showed a reduced collagen-to-elastin ratio, while immunostaining for the receptor for advanced glycation end products was selectively increased in the left anterior descending coronary artery. These data suggest that MetS causes hypertrophic inward remodeling of CRMs and capillary rarefaction, which contribute to decreased coronary flow and myocardial ischemia. Moreover, our data demonstrate novel differential remodeling between coronary micro- and macrovessels in a clinically relevant model of MetS.

Abstract 84: Serum Amyloid A Does Not Modulate the Inverse Association of HDL with Coronary Artery Calcification in Type 2 Diabetes

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Claire K Mulvey ◽  
Timothy W Churchill ◽  
Karen Terembula ◽  
Jane F Ferguson ◽  
Nehal N Mehta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Logistic Regression ◽  
Coronary Artery ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Inverse Association ◽  
Tobit Regression ◽  
Amyloid A

Introduction Although high-density lipoprotein (HDL) is inversely correlated with cardiovascular risk, HDL loses its protective role in pathologic inflammatory states like type 2 diabetes (T2DM). HDL dysfunction contributes to accelerated atherosclerosis in T2DM, but the mechanism is incompletely defined. The acute phase reactant serum amyloid A (SAA) displaces apolipoprotein A-I and may impair HDL-mediated reverse cholesterol efflux. We hypothesized that SAA alters the inverse association between HDL and coronary artery calcium (CAC) in the Penn Diabetes Heart Study, a cross-sectional study of T2DM patients free of overt cardiovascular or renal disease. Methods We measured SAA in serum samples by immunonephelometry (N=975; mean age 58 ± 9 years; 63% male, 57% Caucasian; mean BMI 33 ± 6 kg/m 2 ). HDL was measured enzymatically in lipoprotein fractions after ultracentrifugation. Agatston CAC scores were quantified from electron beam tomography at the same visit. Spearman correlation and logistic regression were used to test associations of SAA with clinical factors and metabolic syndrome. We used Tobit regression to analyze associations between CAC and HDL, both overall and stratified by 3 categories of SAA: undetectable, lower half detectable, and upper half detectable. Results Spearman correlations revealed moderate association of SAA with C-reactive protein (r=0.52) and weak associations of SAA with BMI (r=0.25) and HDL (r=0.17; all p<0.001). In logistic regression, the group with highest SAA levels had increased odds of metabolic syndrome compared to those with undetectable levels (OR 1.56, 95% CI 1.03 to 2.38, p=0.036). In adjusted Tobit regression, HDL was inversely associated with CAC (Tobit coefficient for 1-SD increase in HDL: -0.30; 95% CI -0.54 to -0.06; p=0.013). Across the categories of SAA, however, there was no difference in the association of HDL with CAC (Tobit coefficient for 1-SD increase in HDL: -0.17 [95% CI -0.49 to 0.16] for undetectable vs. -0.31 [95% CI -0.79 to 0.17] for lower half detectable vs. -0.49 [95% CI -1.01 to 0.03] for upper half detectable). Conclusions Despite the association of SAA with metabolic syndrome, these data suggest that elevated SAA may not change the inverse relationship of HDL with CAC in T2DM.

scholarly journals Hyperleptinemia as a Robust Risk Factor of Coronary Artery Disease and Metabolic Syndrome in Type 2 Diabetic Patients

2008 ◽  
Vol 55 (6) ◽  
pp. 1085-1092 ◽  
Author(s):  
Soo-Kyung KIM ◽  
Hae-Jin KIM ◽  
Chul-Woo AHN ◽  
Seok-Won PARK ◽  
Yong-Wook CHO ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Coronary Artery ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Artery Disease ◽  
Type 2 Diabetic

scholarly journals Could osteoprotegerin serve as a marker of metabolic syndrome?

2013 ◽  
Vol 26 (3) ◽  
pp. 309-312
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Urinary Calcium ◽  
Syndrome Type ◽  
Patients With Diabetes ◽  
Artery Disease

There has been a dramatic increase in the worldwide prevalence of obesity, which is associated with the development of several chronic diseases such as metabolic syndrome, type 2 diabetes and cardiovascular diseases. Osteoprotegerin is a glycoprotein mainly secreted by bone but produced also by heart muscle and blood vessels. It inhibits the recruitment, proliferation, and activation of osteoclasts. The role of osteoprotegerin in the pathogenesis of metabolic syndrome, type 2 diabetes and cardiovascular diseases is still discussed. The study was carried out on 62 patients with metabolic syndrome aged 35-83 (34F and 28M). Type 2 diabetes was diagnosed in 76% of subjects and 62% of them suffered from coronary artery disease as a macrovascular complication. Determinations of biochemical parameters and anthropometric measurements were performed in the studied group. The relationships between serum osteoprotegerin concentrations and components of metabolic syndrome and total cholesterol, LDL-cholesterol, HbA1C, BMI, levels of calcium and phosphate in the blood and 24-hour urinary calcium have been analysed. Diabetics had higher osteoprotegerin concentrations than patients without diabetes (5.570 pmol/l vs 4.690 pmol/l). Osteoprotegerin levels in patients with diabetes and coronary artery disease were significantly higher (6.640pmol/l) than in those without macrovascular complications (5.295 pmol/l) (Z=1.986; p=0.047). Furthermore, the associations between osteoprotegerin and calcium and phosphate levels in the blood and 24-hour urinary calcium have been shown. A lower calcium level in the blood was negative but a lower phosphate level was positive correlated with OPG serum concentration (respectively: 6.825 pmol/l vs 5.195 pmol/l, Z=2.656, p=0.008; 4.250pmol/l vs 5.640 pmol/l, Z=2.718, p=0.007). What’s more, the inverse correlations between OPG concentrations and 24-hour urinary calcium and diastolic blood pressure have been observed. No associations between osteoprotegerin and waist circumference, BMI, cholesterol levels and HbA1C, were found. In summary, osteoprotegerin is not a use ful marker of all components of metabolic syndrome. It is level depends on the presence of hypertension, type 2 diabetes and coronary artery disease. This glycoprotein may serve a a marker of calcium and phosphate homeostasis. We concluded that the relationship between osteoprotegerin concentrations and calcification of atherosclerotic plaques in patients with metabolic syndrome and type 2 diabetes should be analysed in further investigations.

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