LMNA messenger RNA expression in highly active antiretroviral therapy-treated HIV-positive patients.
The LMNA gene encodes for lamins A and C as major products, which are involved in nuclear stability, chromatin structure, and gene expression. Several LMNA mutations cause an insulin-resistant lipodystrophy that shares features with HIV-related lipodystrophy. Some HIV-treatment agents alter lamin A/C maturation, organization, and stability in 3T3-L1. We aimed to test the hypothesis that human adipose tissue LMNA expression can be altered in highly active antiretroviral therapy (HAART)-treated HIV-positive patients with lipodystrophy. We have also analyzed both isoforms and explored if their expression is associated with insulin resistance or inflammation in these patients. A cross-sectional study that analyzed abdominal subcutaneous adipose tissue from 39 treated HIV-positive patients (25 of whom had lipodystrophy) and 21 uninfected control subjects was performed. We have observed lower levels of lamin A isoform but normal levels of lamin C isoform in all HIV-infected patients, irrespective of the presence or absence of lipodystrophy, which reinforces the idea that an altered lamin A/C ratio could reflect a pathogenic condition. We have also found a correlation between LMNA adipose expression and several cytokine and adipogenic gene markers in HIV-positive patients, regardless of the presence or absence of lipodystrophy. Hence, in the present study, the lower lamin A expression observed in HIV-positive patients is related to HIV itself or to treatments rather than to the presence of lipodystrophy.
Miranda
Merce
M
Endocrinology and Diabetes Unit, Research Department, University Hospital of Tarragona Joan XXIII, "Pere Virgili" Institute, Rovira i Virgili University, Tarragona, Spain. mmiranda.hj23.ics@gencat.net
Chacón
Matilde R
MR
Vidal
Francesc
F
Megia
Ana
A
Richart
Cristóbal
C
Veloso
Sergi
S
Saumoy
Maria
M
Olona
Carles
C
Vendrell
Joan
J
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D000328:Adult; D000886:Anthropometry; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D014781:Viscera
D016207:Cytokines; C494847:LMNA protein, human; D034904:Lamin Type A; D012333:RNA, Messenger