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Studies of the natural course of the vein graft disease

Studies of the natural course of the vein graft disease with focus on advanced in vivo visualization and improvement of endothelial repair

Project leader Anton Razuavev

Forskare

Anton Razuvaev

Enhet: Kärlkirurgi
E-post: Anton.Razuvaev@ki.se

Researcher

PhD Students

Doktorand

Robert Saxelin

Enhet: Kärlkirurgi
E-post: robert.saxelin@ki.se

Doktorand

Marcus Wannberg

Enhet: Kärlkirurgi
E-post: marcus.wannberg@ki.se

Doktorand

Samuel Röhl

Enhet: Kärlkirurgi
E-post: samuel.rohl@ki.se

Background

Cardiovascular disease is the leading cause of global mortality and physical disability. Vein graft (VG) bypass technique is commonly used for reconstruction of coronary and peripheral circulation. Between 30 and 70% of grafts fail within 5 years due to thrombosis, intimal hyperplasia (IH) and superimposed atherogenesis, processes related to the faulty endothelialization and poor endothelial function. These processes are over represented in patients with metabolic syndrome and high inflammatory state such as in subjects with diabetes, leading to the increased number of life-threatening complications. Although direct effects of glucose presumably play a role, indirect effects via stimulation of RAGE by AGEs formed during hyperglycemia are probably of greater importance.

Objectives

To develop new imaging diagnostic tools for assessment of VG endothelialization. To identify specific local hemodynamic forces, which contribute to the VG failure in different arterial beds and various disorders. We aim also to determine mechanisms in delayed vessel wall repair in subjects with diabetes and thereby facilitate development of therapeutic strategies against restenosis and vein graft failure in this promptly increasing group of the patients.

Methods

The project is based on studies of the local hemodynamic forces and natural course of endothelialization and IH utilizing a translational approach that covers experimental studies with surgical and physiological animal models and a novel high-resolution imaging technology. Experimental results are related to human disease utilizing specimens obtained at surgery through comparative gene- and protein expression pattern analysis of vein graft samples. The project involves also ultrasound examinations and clinical surveillance of vein grafts in human.

Significance

The present study will provide mechanistic insights into the processes of VG failure and contribute to the development of specific and well-timed therapeutic interventions for prevention of the VG disease and therefore reduction of the need for dangerous surgical re-interventions.