Alternative C3 Complement System: Lipids and Atherosclerosis

Autor: Garcia-Arguinzonis, M., Diaz-Riera, Elisa, Peña, Esther, Escate, Rafael, Juan-Babot, Oriol, Mata, P., Badimon, Lina, Padró, Teresa, Universitat Autònoma de Barcelona
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Vascular smooth muscle
Proteome
030204 cardiovascular system & hematology
Muscle
Smooth
Vascular
Extracellular matrix
0302 clinical medicine
cardiovascular disease
Biology (General)
Receptor
Spectroscopy
Cells
Cultured
mass spectrometry
biology
Chemistry
General Medicine
Complement C3
Middle Aged
Computer Science Applications
Cell biology
lipids (amino acids
peptides
and proteins)
Female
medicine.symptom
Adult
QH301-705.5
Integrin
Myocytes
Smooth Muscle
Inflammation
Vascular Remodeling
Catalysis
Article
Inorganic Chemistry
Hyperlipoproteinemia Type II
03 medical and health sciences
Young Adult
proteomics
medicine
Cell Adhesion
Humans
Anaphylatoxin
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
complement system
Wound Healing
Organic Chemistry
Atherosclerosis
Complement system
030104 developmental biology
Case-Control Studies
biology.protein
iC3b
atherosclerosis
Zdroj: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
International Journal of Molecular Sciences
Volume 22
Issue 10
International Journal of Molecular Sciences, Vol 22, Iss 5122, p 5122 (2021)
ISSN: 1422-0067
Popis: Familial hypercholesterolemia (FH) is increasingly associated with inflammation, a phenotype that persists despite treatment with lipid lowering therapies. The alternative C3 complement system (C3), as a key inflammatory mediator, seems to be involved in the atherosclerotic process
however, the relationship between C3 and lipids during plaque progression remains unknown. The aim of the study was to investigate by a systems biology approach the role of C3 in relation to lipoprotein levels during atherosclerosis (AT) progression and to gain a better understanding on the effects of C3 products on the phenotype and function of human lipid-loaded vascular smooth muscle cells (VSMCs). By mass spectrometry and differential proteomics, we found the extracellular matrix (ECM) of human aortas to be enriched in active components of the C3 complement system, with a significantly different proteomic signature in AT segments. Thus, C3 products were more abundant in AT-ECM than in macroscopically normal segments. Furthermore, circulating C3 levels were significantly elevated in FH patients with subclinical coronary AT, evidenced by computed tomographic angiography. However, no correlation was identified between circulating C3 levels and the increase in plaque burden, indicating a local regulation of the C3 in AT arteries. In cell culture studies of human VSMCs, we evidenced the expression of C3, C3aR (anaphylatoxin receptor) and the integrin αMβ2 receptor for C3b/iC3b (RT-PCR and Western blot). C3mRNA was up-regulated in lipid-loaded human VSMCs, and C3 protein significantly increased in cell culture supernatants, indicating that the C3 products in the AT-ECM have a local vessel-wall niche. Interestingly, C3a and iC3b (C3 active fragments) have functional effects on VSMCs, significantly reversing the inhibition of VSMC migration induced by aggregated LDL and stimulating cell spreading, organization of F-actin stress fibers and attachment during the adhesion of lipid-loaded human VSMCs. This study, by using a systems biology approach, identified molecular processes involving the C3 complement system in vascular remodeling and in the progression of advanced human atherosclerotic lesions.
Databáze: OpenAIRE
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