Oxidation and Endothelial Dysfunction Biomarkers of Atherosclerotic Plaque Instability. Studies of the Vascular Wall and Blood

Abstract

The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.

Role of sphingosine-1-phosphate receptor 1 and sphingosine-1-phosphate receptor 2 in hyperglycemia-induced endothelial cell dysfunction

“…One of the hallmarks of endothelial dysfunction is impaired NO bioavailability (23,24). Endothelial dysfunction is characterized by one or more features, including reduced endothelium-mediated vasorelaxation, hemodynamic deregulation, the increased expression of adhesion molecules and inflammatory mediators, the excessive generation of ROS and increased oxidative stress (25)(26)(27). It is widely accepted that ROS play critical roles in vascular EC dysfunction by elevating the calcium concentration in the cytoplasm, reducing both production and vasodilatation (28,29).…”

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

“…This leads to the accumulation of plaque in the coronary arteries that supply blood to the heart or within the aortic arch carrying blood away from the heart. In particular, activated macrophages scavenge ox‐LDL to form foam cells17 that together with cholesterol crystals form stable and unstable plaque, leading to vessel obstruction and plaque rupture, respectively 18, 19. This process results in the narrowing of the arteries specifically at arterial branch points or bifurcations subjected to altered blood flow.…”

“…In particular, activated macrophages scavenge ox-LDL to form foam cells 17 that together with cholesterol crystals form stable and unstable plaque, leading to vessel obstruction and plaque rupture, respectively. 18,19 This process results in the narrowing of the arteries specifically at arterial branch points or bifurcations subjected to altered blood flow. Diabetic patients are 2-4 times more likely to develop major vascular complications as a consequence of atherosclerotic plaque build-up within their arteries.…”

La apoptosis en el Infarto Agudo de Miocardio. Asociación de los polimorfismos Arg72Pro del gen P53 y T309G del gen MDM2 con el tamaño del infarto, la función ventricular izquierda post-infarto y el desarrollo de insuficiencia cardiaca

“…Cuando las células endoteliales son dañadas por diversos estímulos o mediadores inflamatorios, muestran en su superficie moléculas de adhesión de la familia de las selectinas, como la E y la P, y moléculas de adhesión vascular e intercelular, como las VCAM y las ICAM, que son inmediatamente reconocidas por sus respectivos ligandos en las células inflamatorias circulantes 16 . Simultáneamente, las células endoteliales alteradas sintetizan y secretan otras moléculas que atraen más células inflamatorias hacia el lugar de la lesión.…”

“…Simultáneamente, las células endoteliales alteradas sintetizan y secretan otras moléculas que atraen más células inflamatorias hacia el lugar de la lesión. Entre las principales moléculas secretadas se encuentran las citocinas, los factores de crecimiento derivados de las plaquetas (PDGF), factores quimiotácticos, como la proteína 1 quimiotáctica para monocitos (MCP-1) y el fibroblasto básico (bFGF) 16 . Estos fenómenos son comunes en el inicio de cualquier reacción inflamatoria y explican, en el caso de la enfermedad aterosclerótica, el elevado reclutamiento de monocitos en la pared íntima vascular que se observa en las fases iniciales de la formación de las placas ateroscleróticas 16 .…”