Changes of lysosomes in the earliest stages of the development of atherosclerosis

Abstract

One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the ‘normal intima-initial lesion-fatty streak’ sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease.

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

“…Experiments utilizing macrophages in in vitro experiments demonstrated that modified low density lipoproteins (LDL) are captured by macrophages followed by association of vacuoles containing LDL with lysosomes ( Fig. 2A) [10,11]. The molecular mechanisms of interaction of modified LDL with macrophages have been detailed in a large number of reviews [12][13][14][15][16].…”

“…The functional insufficiency of lysosomes is thought to lead to excessive accumulation of lipids ("lipid droplets") in the cytoplasm of macrophages (Fig. 3A, B) [10,18,19]. Eventually, macrophages engulfing modified LDL become overloaded with lipids, and this transforms them into foam cells (Fig.…”

CD68/macrosialin: not just a histochemical marker

“…57 Ultrastructural studies of human atherosclerotic lesions demonstrated that CD68 is mostly located in lysosomes (Figure 3). 58,59 In contrast to macrophages, 59 CD68 is not expressed by dendritic cells (DCs) 14,60 and this helps to immunohistochemically distinguish these two cell types, both of which have antigenpresenting capabilities. Several studies have shown significant upregulation of CD68 expression in macrophages in response to inflammatory stimuli such as exposure to oxLDL 12,49,50 and chronic stimulation with bacterial lipopolysaccharide (LPS) or inflammatory cytokine interferon-γ (IFN-γ).…”

Altered expression of lysosomal hydrolase, acid α-glucosidase, gene in coronary artery disease

“…In human aortic tissues, lysosomal change has been confirmed in the early stage of atherosclerosis [29]. Lysosomal hyrolases and proteins have been involved in lipid and cholesterol metabolisms [30].…”