A subtype of cerebrovascular pericytes is associated with blood-brain barrier disruption that develops during normal aging and simian immunodeficiency virus infection

Neurobiol Aging. 2020 Dec;96:128-136. doi: 10.1016/j.neurobiolaging.2020.08.006. Epub 2020 Aug 17.

Abstract

Lax phenotypic characterization of these morphologically distinct pericytes has delayed our understanding of their role in neurological disorders. We herein establish markers which uniquely distinguish different subpopulations of human brain microvascular pericytes and characterize them independently from cerebrovascular smooth muscle cells. Furthermore, we begin to elucidate the roles of these subsets in blood-brain barrier (BBB) breakdown by studying natural aging and simian immunodeficiency virus (SIV) infection in rhesus macaques. We demonstrate that the main type-1 pericyte subpopulation in the brain of young uninfected adults is positive for platelet-derived growth factor receptor-β (PDGFRB) and negative for α-smooth muscle actin (SMA) and myosin heavy chain 11 (MYH11), whereas PDGFRB+/SMA+/MYH11- (type-2) pericytes are found more frequently in older adults and are associated with SIV infection and progression. Interestingly, we find a strong positive correlation between the degree of BBB breakdown and the percentage of type-2 pericytes regardless of age or SIV status. Taken together, our findings suggest that type-2 pericytes may be a cellular biomarker related to BBB disruption independent of disease status.

Keywords: Aging; Brain; HIV; Pericyte; Smooth muscle cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Adult
  • Aging / pathology*
  • Animals
  • Blood-Brain Barrier / pathology*
  • Brain / blood supply
  • Humans
  • Macaca mulatta
  • Microvessels / cytology
  • Myosin Heavy Chains / metabolism
  • Pericytes / classification*
  • Pericytes / metabolism
  • Pericytes / physiology*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Simian Acquired Immunodeficiency Syndrome / pathology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus*
  • Young Adult

Substances

  • Actins
  • Receptor, Platelet-Derived Growth Factor beta
  • Myosin Heavy Chains