Obesity Inhibits Angiogenesis Through TWIST1-SLIT2 Signaling. Front Cell Dev Biol 2021;9:693410
Date
10/19/2021Pubmed ID
34660572Pubmed Central ID
PMC8511494DOI
10.3389/fcell.2021.693410Scopus ID
2-s2.0-85116933380 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Angiogenesis is required for functional adipose tissue maintenance, remodeling, and expansion. Physiologically balanced adipogenesis and angiogenesis are inhibited in subcutaneous adipose tissue in obese humans. However, the mechanism by which angiogenesis is inhibited in obese adipose tissue is not fully understood. Transcription factor TWIST1 controls angiogenesis and vascular function. TWIST1 expression is lower in obese human adipose tissues. Here, we have demonstrated that angiogenesis is inhibited in endothelial cells (ECs) isolated from adipose tissues of obese humans through TWIST1-SLIT2 signaling. The levels of TWIST1 and SLIT2 are lower in ECs isolated from obese human adipose tissues compared to those from lean tissues. Knockdown of TWIST1 in lean human adipose ECs decreases, while overexpression of TWIST1 in obese adipose ECs restores SLIT2 expression. DNA synthesis and cell migration are inhibited in obese adipose ECs and the effects are restored by TWIST1 overexpression. Obese adipose ECs also inhibit blood vessel formation in the gel subcutaneously implanted in mice, while these effects are restored when gels are mixed with SLIT2 or supplemented with ECs overexpressing TWIST1. These findings suggest that obesity impairs adipose tissue angiogenesis through TWIST1-SLIT2 signaling.
Author List
Hunyenyiwa T, Hendee K, Matus K, Kyi P, Mammoto T, Mammoto AAuthors
Kathryn Hendee in the CTSI department at Medical College of Wisconsin - CTSIAkiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
