Cysteine-Rich LIM-Only Protein 4 (CRP4) Promotes Atherogenesis in the ApoE-/- Mouse Model.
Cells
; 11(8)2022 04 17.
Article
em En
| MEDLINE
| ID: mdl-35456043
ABSTRACT
Vascular smooth muscle cells (VSMCs) can switch from their contractile state to a synthetic phenotype resulting in high migratory and proliferative capacity and driving atherosclerotic lesion formation. The cysteine-rich LIM-only protein 4 (CRP4) reportedly modulates VSM-like transcriptional signatures, which are perturbed in VSMCs undergoing phenotypic switching. Thus, we hypothesized that CRP4 contributes to adverse VSMC behaviours and thereby to atherogenesis in vivo. The atherogenic properties of CRP4 were investigated in plaque-prone apolipoprotein E (ApoE) and CRP4 double-knockout (dKO) as well as ApoE-deficient CRP4 wildtype mice. dKO mice exhibited lower plaque numbers and lesion areas as well as a reduced content of α-smooth muscle actin positive cells in the lesion area, while lesion-associated cell proliferation was elevated in vessels lacking CRP4. Reduced plaque volumes in dKO correlated with significantly less intra-plaque oxidized low-density lipoprotein (oxLDL), presumably due to upregulation of the antioxidant factor peroxiredoxin-4 (PRDX4). This study identifies CRP4 as a novel pro-atherogenic factor that facilitates plaque oxLDL deposition and identifies the invasion of atherosclerotic lesions by VSMCs as important determinants of plaque vulnerability. Thus, targeting of VSMC CRP4 should be considered in plaque-stabilizing pharmacological strategies.
Palavras-chave
3',5'-cyclic guanosine monophosphate (cGMP); 3',5'-cyclic guanosine monophosphate-dependent protein kinase type I (cGKI); Calponin and LIM domain containing 2 (MICAL2); acyl-CoA dehydrogenase long chain (ACADL); apolipoprotein E (ApoE); cysteine-rich LIM-only protein 4 (CRP4); microtubule associated monooxygenase; peroxiredoxin-4 (PRDX4); pirin (PIR)
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Aterosclerose
/
Placa Aterosclerótica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cells
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha