HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Alternative C3 Complement System: Lipids and Atherosclerosis.

Abstract
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.
AuthorsMaisa Garcia-Arguinzonis, Elisa Diaz-Riera, Esther Peña, Rafael Escate, Oriol Juan-Babot, Pedro Mata, Lina Badimon, Teresa Padro
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 10 (May 12 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34066088 (Publication Type: Journal Article)
Chemical References
  • Complement C3
  • Proteome
Topics
  • Adult
  • Atherosclerosis (immunology, metabolism, pathology)
  • Case-Control Studies
  • Cell Adhesion
  • Cells, Cultured
  • Complement C3 (metabolism)
  • Female
  • Humans
  • Hyperlipoproteinemia Type II (immunology, metabolism, pathology)
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular (immunology, metabolism, pathology)
  • Myocytes, Smooth Muscle (immunology, metabolism, pathology)
  • Proteome (analysis, metabolism)
  • Vascular Remodeling
  • Wound Healing
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: