Your browser doesn't support javascript.
loading
CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis.
Bao, Qiankun; Zhang, Bangying; Zhou, Lu; Yang, Qian; Mu, Xiaofeng; Liu, Xing; Zhang, Shiying; Yuan, Meng; Zhang, Yue; Che, Jingjin; Wei, Wen; Liu, Tong; Li, Guangping; He, Jinlong.
Afiliação
  • Bao Q; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Zhang B; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Zhou L; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Yang Q; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Mu X; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Liu X; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Zhang S; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Yuan M; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Zhang Y; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Che J; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Wei W; Center for Mechanisms of Evolution, Biodesign Institute, Arizona State University, Tempe (W.W.).
  • Liu T; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • Li G; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, China (Q.B., B.Z., L.Z., Q.Y., X.M., X.L., S.Z., M.Y., Y.Z., J.C., T.L., G.L.).
  • He J; Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Physiology and Pathophysiology, Tianjin Medical University, China (J.H.).
Circ Res ; 134(8): e72-e91, 2024 Apr 12.
Article em En | MEDLINE | ID: mdl-38456298
ABSTRACT

BACKGROUND:

CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms.

METHODS:

Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE-/-) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism.

RESULTS:

We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE-/- mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain-containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation.

CONCLUSIONS:

Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aterosclerose / Placa Aterosclerótica Limite: Animals / Humans Idioma: En Revista: Circ Res Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aterosclerose / Placa Aterosclerótica Limite: Animals / Humans Idioma: En Revista: Circ Res Ano de publicação: 2024 Tipo de documento: Article