Effect of metabolic syndrome on the response to arterial injury

Abstract

Background Metabolic syndrome is now an epidemic in the US population. Intimal hyperplasia remains the principal lesion in the development of restenosis after vessel wall injury. The aim of this study is to characterize the changes induced in wall morphology in the developing intimal hyperplasia within a murine model in the presence of diabetes (type 1) and metabolic syndrome. Methods Control (wild-type B6), Diabetic Type 1 (NOD) and Metabolic Syndrome (RCS-10) mice were used. The murine femoral wire injury model was employed in which a micro wire is passed through a branch of the femoral and used to denude the common femoral and iliac arteries. Specimens were perfusion-fixed and sections were stained with H&E and Movat’s stains such that dimensional and compositional morphometry could be performed using an ImagePro system. Additional stains for proliferation and apoptosis were employed. Results In control mice, the injured femoral arteries develop intimal hyperplasia, which is maximal at 28 days and remains stable to day 56. Sham-operated vessels do not produce such a response. In diabetic mice, the intimal response increased 5-fold with a 2-fold increase in proteoglycan deposition, while in the metabolic syndrome mice there was a 6-fold increase in the intimal response and a similar increase in proteoglycan deposition. Collagen deposition was different, with a 22-fold increase over control in collagen deposition in diabetes and a 100-fold increase over control in collagen deposition in metabolic syndrome as compared to the control injury mice. Maximal vascular smooth muscle cell (VSMC) proliferation was decreased in both diabetes and metabolic syndrome compared to controls, while early cell apoptosis in both diabetes and metabolic syndrome was sustained over a longer period of time compared to wild-type mice. Conclusions These data demonstrate that development of intimal hyperplasia is markedly different in diabetes and metabolic syndrome compared to controls, with an increase in collagen deposition, a reduction in VSMC proliferation and an increase in early VSMC apoptosis. These findings suggest that preventative strategies against restenosis must be tailored for the diabetic and metabolic syndrome patients.

RING finger protein 10 attenuates vascular restenosis by inhibiting vascular smooth muscle cell hyperproliferation in vivo and vitro

“…Neointimal hyperplasia is markedly enhanced in vascular restenosis, which is ascribed to VSMC hyperproliferation . The multiple cardiovascular risk factors associated with MetS also significantly promote these pathological processes .Therefore, we establish a HF + BI model in vivo and a HG model in vitro to investigate vascular restenosis based on these pathological backgrounds of MetS.…”

Nicorandil attenuates carotid intimal hyperplasia after balloon catheter injury in diabetic rats

“…Intimal hyperplasia arises from an initial injury to the artery. Diabetes enhances cellular proliferation, adhesion molecular expression and inflammatory cell infiltration after arterial injury in multiple animal models [ 24 ]. Diabetic rats respond to vascular injury with increased influx of inflammatory cells, enhanced proliferative activity and greater intima formation compared with non diabetic rats [ 25 ].…”

“…Diabetic rats respond to vascular injury with increased influx of inflammatory cells, enhanced proliferative activity and greater intima formation compared with non diabetic rats [ 25 ]. In vitro, high glucose promotes VSMCs migration and proliferation by increasing integrins, advanced glycation end products and glycoproteins [ 24 ]. Several anti-diabetic therapies have been found to inhibit intimal hyperplasia after balloon injury in preclinical model.…”

Platelet-Derived Extracellular Vesicles Increase Col8a1 Secretion and Vascular Stiffness in Intimal Injury

“…Alterations in extracellular matrix composition and arterial geometry result in structural arterial stiffness ( Namba et al, 2019 ). In a murine femoral wire injury model associated with intimal hyperplasia, there is substantial collagen and proteoglycan deposition ( Fu et al, 2014 ), which may cause changes in vascular stiffness. In addition, collagen type I ( Lee et al, 2009 ; Kanshana et al, 2018 ), type III ( Kanshana et al, 2018 ), type VIII ( Plenz et al, 1999 ) and fibronectin ( Yao et al, 2009 ) are upregulated in different animal intimal injury models.…”