Experimental Metabolic Syndrome Model Associated with Mechanical and Structural Degenerative Changes of the Aortic Valve

Abstract

The purpose of this study was to test the hypothesis that an experimental high fat (HF) animal with metabolic syndrome results in structural degeneration of the aortic valve. Domestic pigs were divided (n = 12) and administered either a normal or HF diet. After 16-weeks, the HF diet group had increased weight (p ≤ 0.05), total cholesterol (p ≤ 0.05), and systolic and diastolic pressure (p ≤ 0.05). The aortic valve extracellular matrix showed loss of elastin fibers and increased collagen deposition in the HF diet group. Collagen was quantified with ELISA, which showed an increased concentration of collagen types 1 and 3 (p ≤ 0.05). In the HF diet group, the initial stages of microcalcification were observed. Uniaxial mechanical testing of aortic cusps revealed that the HF diet group expressed a decrease in ultimate tensile strength and elastic modulus compared to the control diet group (p ≤ 0.05). Western blot and immunohistochemistry indicated the presence of proteins: lipoprotein-associated phospholipase A2, osteopontin, and osteocalcin with an increased expression in the HF diet group. The current study demonstrates that experimental metabolic syndrome induced by a 16-week HF diet was associated with a statistically significant alteration to the physical architecture of the aortic valve.

Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications

“…In patients with the bicuspid aortic valve, which is the most common congenital heart disease occurring in 1%-2% of the population, AS development occurs statistically more frequently [2]. Growing evidence indicates that diabetes mellitus (DM) can increase the risk of AS development and the rate of AS progression [4][5][6][7][8][9][10][11]. The diagnosis of AS is based on echocardiographic assessment.…”

Diet-Induced Rabbit Models for the Study of Metabolic Syndrome

“…On the other hand, canine models do not show all the components of MetS because the development of endothelial damage or fasting hyperglycaemia in dogs is questionable. In addition, porcine models present high anatomical and physiological similarity with humans [18,21,22]. Therefore, they can offer significant predictive power for MetS components, but their maintenance and need for trained personnel and complex resources for experimental procedures make porcine models very laborious and expensive to use [16].…”

Diabetes Mellitus and Its Implications in Aortic Stenosis Patients

“…These alterations occur simultaneously, increasing the risk of adverse events and leading to the association of metabolic syndrome with the progression of DAS irrespective of traditional risk factors [73]. Furthermore, experimental models have demonstrated that metabolic syndrome is as-sociated with mechanical and structural changes of the AV and early calcification [74]. Alternatively, there are reports that patients with metabolic syndrome manifest a greater risk of developing DM [75].…”