title: Analysis of the effects of HIV-1 Tat on the survival and differentiation of vessel wall-derived mesenchymal stem cells.
abstract: HIV infection is an independent risk factor for atherosclerosis development and cardiovascular damage. As vessel wall mesenchymal stem cells (MSCs) are involved in the regulation of vessel structure homeostasis, we investigated the role of Tat, a key factor in HIV replication and pathogenesis, in MSC survival and differentiation. The survival of subconfluent MSCs was impaired when Tat was added at high concentrations (200-1,000 ng/ml), whereas lower Tat concentrations (1-100 ng/ml) did not promote apoptosis. Tat enhanced the differentiation of MSC toward adipogenesis by the transcription and activity upregulation of PPARγ. This Tat-related modulation of adipogenesis was tackled by treatment with antagonists of Tat-specific receptors such as SU5416 and RGD Fc. In contrast, Tat inhibited the differentiation of MSCs to endothelial cells by downregulating the expression of VEGF-induced endothelial markers such as Flt-1, KDR, and vWF. The treatment of MSCs with Tat-derived peptides corresponding to the cysteine-rich, basic, and RGD domains indicated that these Tat regions are involved in the inhibition of endothelial marker expression. The Tat-related impairment of MSC survival and differentiation might play an important role in vessel damage and formation of the atherosclerotic lesions observed in HIV-infected patients.
authors.affiliation: Microbiology Section, Department of Haematology and Oncological Sciences, University of Bologna, Bologna, Italy. davide.gibellini@unibo.it
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.forename: Anna
authors.initials: A
authors.lastname: Miserocchi
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Tazzari
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Alberto
authors.initials: A
authors.lastname: Clò
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.forename: Cristina
authors.initials: C
authors.lastname: Ponti
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.forename: Pasqualepaolo
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Marco
authors.initials: M
authors.lastname: Borderi
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
mesh_terms: D000328:Adult; D017209:Apoptosis; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015696:Gene Products, tat