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Normal and reconstituted high-density lipoprotein protects differentiated monocytes from oxidized low-density lipoprotein-induced apoptosis.

Authors
  • Kaur, Navkiran1
  • Kumari, Savita2
  • Ghosh, Sujata3
  • 1 Assistant Professor, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India. , (India)
  • 2 Professor, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India. , (India)
  • 3 Professor, Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. , (India)
Type
Published Article
Journal
ARYA atherosclerosis
Publication Date
Nov 01, 2020
Volume
16
Issue
6
Pages
269–277
Identifiers
DOI: 10.22122/arya.v16i6.1582
PMID: 34122580
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The progression of atherosclerosis is an ongoing struggle between cell division and cell death. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a novel receptor for oxidized low-density lipoprotein (ox-LDL), mediates ox-LDL-induced apoptosis of monocytes. The anti-atherogenic function of plasma high-density lipoprotein (HDL) includes the ability to inhibit apoptosis of macrophage, although the exact mechanism and consequences of apoptosis in the development and progression of this disease are still controversial. Thus, in the present study, the effect of normal HDL (nHDL) and reconstituted HDL (rHDL) on ox-LDL-induced cellular responses in differentiated monocytes in view of apoptosis and LOX-1 receptor expression was investigated. The expression of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), caspase-3, and cytochrome c (cyt c) was assessed and substantiated in 30 hyper-LDL and control subjects. To assess the expression of LOX-1 on differentiated THP-1 cells, western blotting was carried out, followed by statistical analysis in 30 patients and control subjects. nHDL/rHDL inhibited the ox-LDL-induced apoptosis in the differentiated human monocytic cells, THP-1 cells, and differentiated monocytes of patient and control subjects. Enhanced expression of scavenger receptor, LOX-1, in the differentiated monocytes was also downregulated in presence of nHDL/rHDL. nHDL/rHDL could inhibit the ox-LDL-induced mitochondrial apoptotic pathway and aberrant expression of LOX-1 in patients. Double immunostaining using fluorescein isothiocyanate (FITC)-conjugated ox-LDL and LOX-1 in apoptotic cells indicates its significant role in the differentiated monocytes. It was observed that nHDL/rHDL could promote macrophage survival by preserving mitochondrial integrity from ox-LDL-induced apoptosis. © 2020 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.

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