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

Understanding the Heterogeneity of Human Pericyte Subsets in Blood-Brain Barrier Homeostasis and Neurological Diseases

“…This same study found that PC1 expressing VCAM1 and CD274 could distinguish PC1 from the DLK1expressing PC2 [45]. The use of SMA and MYH11 in combination as distinguishing markers was recently confirmed in vivo when a PDGFRB+/SMA−/MYH11− phenotype was successfully used to identify PC1, PDGFRB+/SMA+/MYH11− for PC2, and PDGFRB+/SMA+/MYH11+ marked only VSMCs in the brains of rhesus macaques and humans [48].…”

“…Reaching a better understanding of the functional differences between PC1 and PC2 can be achieved by studying their presence in various states of BBB homeostasis and disease. PC1 fit the traditional description of BBB-supportive microvascular PCs, while being the most abundant subpopulation found in young healthy individuals [7,48]. They are rarely associated with areas of fibrinogen extravasation, but are associated with an organized and regulated basement membrane and astrocytic endfoot arrangements [7,48].…”

“…In our recent study examining PCs in the brains of humans and nonhuman primates, it was found that uninfected infant rhesus macaques demonstrated few to no PC2 in cortical tissue, which contains almost exclusively capillary PC1 [48]. While PC populations shift during aging or simian immunodeficiency virus infection from PC1 to PC2-dominant populations, the total number of PCs remains largely unchanged except in the most advanced stages of disease where PC loss is observed [7,48].…”

“…In addition to the complexities of identifying PC from other vascular and perivascular cell types, a pathological subset of neurovascular PCs has recently been identified [7,48]. Following nomenclature set by the cancer field, physiological capillary PCs were termed Type-1 Pericytes (PC1), while the pathological subset of these capillary PCs were termed Type-2 Pericytes (PC2) [48,49]. Both subsets can be found on brain capillary vessels of less than 10 µm in luminal diameter and of the same branching order, but whether these correspond to mesh PCs or thinstrand PCs is unclear [48].…”

“…One explanation for a series of conflicting reports in literature on the presence of SMA in capillary PCs would be the presence of a SMA+ pathogenic PC subtype [53,54]. More recent studies have elucidated more information on the differences between these two PC subtypes [45,48,55]. One study identified two distinct, but unnamed PC subsets, one which is CD90-positive with limited expression of SMA, and one being CD90-negative with higher expression of SMA and PDGFRB [55].…”