Class A scavenger receptor deficiency augments angiotensin II-induced vascular remodeling

Biochem Pharmacol. 2014 Aug 1;90(3):254-64. doi: 10.1016/j.bcp.2014.05.015. Epub 2014 May 27.

Abstract

Class A scavenger receptor (SR-A) is a multifunctional molecule that participates in macrophage-mediated inflammation. Here we evaluated the role of SR-A in angiotensin II (Ang II)-induced hypertensive vascular remodeling. Chronic infusion of Ang II leads to an increased systolic blood pressure both in SR-A knockout (SR-A(-/-)) and wild type (SR-A(+/+)) mice with no significant difference between these two groups. SR-A(-/-) hypertensive mice, however, exhibited a marked augmentation of arterial wall thickening and vascular cell proliferation compared with SR-A(+/+) hypertensive mice. M1 macrophage markers were increased whereas M2 macrophage markers were decreased in vascular tissues of SR-A(-/-) mice. Co-culture experiments revealed that more pro-inflammatory cytokines like TNF-α were produced by SR-A(-/-) peritoneal macrophages leading to a stronger proliferation of primary vascular smooth muscle cells in vitro. In addition, SR-A(-/-) macrophages were more prone to lipopolysaccharide-induced M1 differentiation while resisting interleukin-4-induced M2 differentiation. Importantly, transplantation of SR-A(-/-) bone marrow into SR-A(+/+) mice significantly augmented Ang II-induced vascular remodeling. These results show that SR-A is critical for Ang II-induced vascular remodeling by regulating macrophage polarization. Therefore, SR-A may be a useful therapeutic target for the intervention of hypertensive vascular remodeling.

Keywords: BAY 11-708 (PubChem CID: 24891842); Hypertension; Inflammation; Macrophage polarization; Pentoxifylline (PubChem CID: 4740); SR-A; Teriflunomide (PubChem CID: 4651473); Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage
  • Angiotensin II / adverse effects
  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / immunology
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Blood Vessels / immunology
  • Blood Vessels / metabolism
  • Blood Vessels / pathology*
  • Cell Proliferation
  • Cell Transdifferentiation
  • Cells, Cultured
  • Coculture Techniques
  • Crosses, Genetic
  • Disease Models, Animal*
  • Hypertension / physiopathology*
  • Infusions, Intravenous
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred ICR
  • Mice, Knockout
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Neovascularization, Pathologic / etiology*
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Scavenger Receptors, Class A / deficiency
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism*
  • Transplantation Chimera / immunology
  • Transplantation Chimera / metabolism

Substances

  • Msr1 protein, mouse
  • Scavenger Receptors, Class A
  • Angiotensin II