1. Dendritic Cells Expressing Triggering Receptor Expressed on Myeloid Cells-1 Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis
- Author
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Devendra K. Agrawal, Vikrant Rai, Zhifei Shao, and Velidi H. Rao
- Subjects
0301 basic medicine ,Male ,Pathology ,Myeloid ,Necrosis ,Physiology ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Pathology and Laboratory Medicine ,Vascular Medicine ,Monocytes ,White Blood Cells ,0302 clinical medicine ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Carotid Stenosis ,Receptors, Immunologic ,Receptor ,lcsh:Science ,Immune Response ,Stenosis ,Endarterectomy, Carotid ,Innate Immune System ,Multidisciplinary ,Membrane Glycoproteins ,biology ,T Cells ,Plaque, Atherosclerotic ,3. Good health ,medicine.anatomical_structure ,Cytokines ,Female ,medicine.symptom ,Cellular Types ,Research Article ,medicine.medical_specialty ,Immune Cells ,Immunology ,Inflammation ,Proinflammatory cytokine ,Lesion ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,medicine ,Humans ,RNA, Messenger ,Fascin ,Innate immune system ,Blood Cells ,business.industry ,Macrophages ,lcsh:R ,Biology and Life Sciences ,Dendritic Cells ,HLA-DR Antigens ,Cell Biology ,Molecular Development ,Atherosclerosis ,Actins ,Triggering Receptor Expressed on Myeloid Cells-1 ,030104 developmental biology ,Case-Control Studies ,Immune System ,biology.protein ,lcsh:Q ,business ,Developmental Biology - Abstract
Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory cells, including T-lymphocytes, dendritic cells (DCs) and macrophages that are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. In atherosclerotic tissue the number of DCs increases with the progression of the lesion and produce several inflammatory cytokines and growth factors. Triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role in inflammation. However, relationship of DCs and the role of TREM-1 with the stability of atherosclerotic plaques have not been examined. In this study, we investigated the heterogeneity of the plaque DCs, myeloid (mDC1 and mDC2) and plasmacytoid (pDCs), and examined the expression of TREM-1 and their co-localization with DCs in the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. We found increased expression of HLA-DR, fascin, and TREM-1 and decreased expression of TREM-2 and α-smooth muscle actin in S compared to AS atherosclerotic carotid plaques. Both TREM-1 and fascin were co-localized suggesting increased expression of TREM-1 in plaque DCs of S compared to AS patients. These data were supported by increased mRNA transcripts of TREM-1 and decreased mRNA transcripts of TREM-2 in carotid plaques of S compared to AS patients. There was higher density of both CD1c+ mDC1 and CD141+ mDC2 in the carotid plaques from AS compared to S patients, where as the density of CD303+ pDCs were higher in the carotid plaques of S compared to AS patients. These findings suggest a potential role of pDCs and TREM-1 in atherosclerotic plaque vulnerability. Thus, newer therapies could be developed to selectively block TREM-1 for stabilizing atherosclerotic plaques.
- Published
- 2016