ABSTRACT
OxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL-8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry. Pearson tests were used to investigate potential correlation between (a) different gene expressions and (b) gene expression and patient's plasma constituents. CD36, SRA, ADFP, and IL-8 were shown to be significantly more expressed in PLA compared to NPLA. In PLA, a significant correlation was observed between CD36, SRA, ADFP, and IL-8 mRNA levels. Moreover, CD36 expression level was significantly inversely correlated to plasma marker ApoAI. The above investigated genes/proteins may play a key role in the maturation of atherosclerotic lesions.
Subject(s)
Apolipoprotein A-I/blood , CD36 Antigens/metabolism , Carotid Stenosis/genetics , Carotid Stenosis/metabolism , Membrane Proteins/metabolism , CD36 Antigens/genetics , Cell Line, Tumor , Cholesterol, HDL/blood , Down-Regulation/drug effects , Endarterectomy, Carotid , Gene Expression/drug effects , Humans , Interleukin-8/genetics , Interleukin-8/metabolism , Lipoproteins, LDL/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Membrane Proteins/genetics , Perilipin-2 , RNA, Messenger/analysis , Scavenger Receptors, Class A/genetics , Scavenger Receptors, Class A/metabolism , Up-Regulation/drug effectsABSTRACT
As a result of vascular injury, activated platelets will rapidly interact with circulating platelets, via membrane glycoprotein complex alphaIIbbeta3 (GPIIb-IIIa) and fibrinogen, to form a thrombus or a plug preventing fatal bleeding. In addition, platelets interacting with ruptured atherosclerotic plaques or with the surface of diseased vessels can aggregate and induce ischemia that prevents blood flow. However, increasing evidence has also shown that circulating platelets interact with leukocytes and endothelial cells, via specific adhesion molecules, in inflammation, vascular remodelling and thrombosis. The aim of this chapter is to present the importance of cell-cell interactions involving platelets and leukocytes in events related to inflammation, coagulation, vascular remodelling and thrombosis. A key adhesion molecule implicated in platelet interaction with leukocytes is P-selectin, also known as CD62P. It is present on activated platelets and endothelial cells, and its counterpart on leukocytes is known as P-selectin glycoprotein ligand-1 (PSGL-1). A critical co-factor leading to leukocyte activation in platelet-monocyte aggregate formation is the presence of a chemokine known as RANTES. It acts in concert with platelet P-selectin and PSGL-1 in monocyte stimulation.
Subject(s)
Thrombosis/pathology , Animals , Blood Platelets/metabolism , Cell Adhesion , Cell Communication , Endothelium, Vascular/metabolism , Humans , Inflammation , Ischemia , Leukocytes/metabolism , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Models, Biological , Monocytes/metabolism , P-Selectin/chemistry , P-Selectin/genetics , Platelet Aggregation , Platelet Glycoprotein GPIIb-IIIa Complex/chemistryABSTRACT
INTRODUCTION: The aim of this work was to identify new renin target genes in left ventricular hypertrophy during hypertension. MATERIALS AND METHODS: We compared left ventricle gene expression from four transgenic TGR(mRen2)27 (TG+/-) rats and four non-transgenic littermates (TG-/-) using cDNA macroarray. Hybridisation signals were quantified with a phosphorimager, and normalised to an external scale. Data analysis was performed with Statistical Analysis for Microarrays (SAM 1.21) software. The mRNA levels of candidate genes were determined by semi-quantitative RT-PCR in three different hypertensive rats: TG+/-, spontaneously hypertensive (SHR) and genetically Lyon hypertensive (LH) rats, compared to their respective controls (TG-/-, Wistar-Kyoto, Lyon low blood pressure rats). RESULTS: Out of 1,200 genes present on the macroarray, 233 were reliably measured and only three were overexpressed (Biglycan, beta1-adenosine monophosphate-activated protein kinase [AMPK] and amyloid precursor like protein 2 [APLP2]) and 19 were underexpressed in the left ventricle of TG+/- compared with TG-/-. APLP2 is a member of the amyloid precursor protein (APP) family. APLP2 and APP mRNA levels were increased in TGR(mRen2)27 but significantly decreased in LH rats, while only APP was increased in SHR rats. CONCLUSIONS: We report new genes associated with renin-dependent left ventricular hypertrophy. Moreover, this work shows for the first time that the APP family gene expression could be altered in response to high renin activity and this effect is independent of cardiac remodelling and hypertension.
