Intermedin1-53 Ameliorates Homocysteine-Promoted Atherosclerotic Calcification by Inhibiting Endoplasmic Reticulum Stress.
J Cardiovasc Pharmacol Ther
; 25(3): 251-264, 2020 05.
Article
de En
| MEDLINE
| ID: mdl-31698947
ABSTRACT
AIM:
Vascular calcification (VC) is thought to be an independent predictor of cardiovascular morbidity and mortality. Intermedin1-53 (IMD) is a cardiovascular protective peptide and can inhibit vascular medial calcification in rats. In this study, we investigated the effect of IMD on atherosclerotic calcification induced by a high-fat diet plus homocysteine (Hcy) and the potential mechanisms.METHODS:
ApoE-/- mice were fed a high-fat diet with Hcy in drinking water to induce atherosclerotic calcification.RESULTS:
As compared to the high-fat diet alone, Hcy treatment significantly increased atherosclerotic lesion areas and the number of calcified nodules in aortic roots and was reduced by IMD infusion or 4-phenylbutyric acid (PBA) treatment. In vitro, as compared to calcifying medium alone, Hcy treatment further increased alkaline phosphatase activity, calcium content, and calcium nodule number in human aorta vascular smooth muscle cells (HA-VSMCs), all blocked by IMD or PBA pretreatment. Mechanistically, IMD or PBA significantly alleviated endoplasmic reticulum stress (ERS) activation compared with Hcy treatment. In parallel, IMD or PBA attenuated the messenger RNA levels of osteogenic markers and inflammatory cytokines in aortas and their protein levels in lesions of aortic roots. In vitro, Hcy treatment significantly increased the protein levels of osteoblast-like cell markers in primary rat VSMCs and inflammation markers in mouse peritoneal macrophages, all decreased with IMD or PBA pretreatment. Intermedin1-53 pretreatment also markedly reduced the protein levels of ERS markers in rat VSMCs and mouse peritoneal macrophages.CONCLUSIONS:
Intermedin1-53 protects against Hcy-promoted atherosclerotic calcification in ApoE-/- mice by inhibiting ERS.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladies de l'aorte
/
Myocytes du muscle lisse
/
Hormones peptidiques
/
Athérosclérose
/
Calcification vasculaire
/
Stress du réticulum endoplasmique
/
Homocystéine
/
Muscles lisses vasculaires
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
J Cardiovasc Pharmacol Ther
Sujet du journal:
ANGIOLOGIA
/
CARDIOLOGIA
/
FARMACOLOGIA
Année:
2020
Type de document:
Article
Pays d'affiliation:
Chine