Nicola Squillace1, Elena Bresciani2, Antonio Torsello2, Alessandra Bandera3, Francesca Sabbatini3, Chiara Giovannetti2, Giuseppe Giunta4, Luca Rovati4, Massimo Del Bene4, Vittorio Locatelli2, Andrea Gori5. 1. Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, Monza, Italy n.squillace@hsangerardo.org. 2. Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy. 3. Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, Monza, Italy. 4. Plastic Surgery Unit, San Gerardo Hospital, Monza, Italy. 5. Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, Monza, Italy Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
Abstract
OBJECTIVES: We evaluated the possibility that a pattern of abnormal microRNA (miRNA) expression could be fuelling the mechanisms causing HIV-associated lipodystrophy (HAL). METHODS: In this case-control study, samples of subcutaneous adipose tissue from eight consecutive HIV-infected patients on combination antiretroviral therapy with HAL (cases) were compared with those of eight HIV-negative subjects (controls). Human miRNA microarrays were used to probe the transcriptomes of the samples. Analysis of differentially expressed miRNAs was performed using DataAssist v2.0 software, applying a paired Student's t-test. RESULTS: Data showed that 21 miRNAs out of 754 were overexpressed in the patient group. Ten of these (i.e. miR-186, miR-199a-3p, miR-214, miR-374a, miR-487b, miR-532-5p, miR-628-5p, miR-874, miR-125-b-1* and miR-374b*) were up-regulated to a significant degree (fold change >2.5; P < 0.01). Eleven other miRNAs (i.e. miR-let-7d, miR-24, miR-30c, miR-125a-3p, miR-149, miR-191, miR-196-b, miR-218, miR-342-3p, miR-452 and miR-454*) were 2- to 2.5-fold more expressed in HIV+ samples than in controls. Levels of mRNA for lipin 1, the target of miR-218, were significantly lower in subcutaneous adipose tissue from HIV patients. CONCLUSIONS: In adipocytes of HIV-infected patients, the up-regulation of specific miRNAs could lead to an increased 'activation' that might contribute to the pathogenesis of HAL by increasing cell turnover and/or promotion of apoptosis.
OBJECTIVES: We evaluated the possibility that a pattern of abnormal microRNA (miRNA) expression could be fuelling the mechanisms causing HIV-associated lipodystrophy (HAL). METHODS: In this case-control study, samples of subcutaneous adipose tissue from eight consecutive HIV-infectedpatients on combination antiretroviral therapy with HAL (cases) were compared with those of eight HIV-negative subjects (controls). Human miRNA microarrays were used to probe the transcriptomes of the samples. Analysis of differentially expressed miRNAs was performed using DataAssist v2.0 software, applying a paired Student's t-test. RESULTS: Data showed that 21 miRNAs out of 754 were overexpressed in the patient group. Ten of these (i.e. miR-186, miR-199a-3p, miR-214, miR-374a, miR-487b, miR-532-5p, miR-628-5p, miR-874, miR-125-b-1* and miR-374b*) were up-regulated to a significant degree (fold change >2.5; P < 0.01). Eleven other miRNAs (i.e. miR-let-7d, miR-24, miR-30c, miR-125a-3p, miR-149, miR-191, miR-196-b, miR-218, miR-342-3p, miR-452 and miR-454*) were 2- to 2.5-fold more expressed in HIV+ samples than in controls. Levels of mRNA for lipin 1, the target of miR-218, were significantly lower in subcutaneous adipose tissue from HIV patients. CONCLUSIONS: In adipocytes of HIV-infectedpatients, the up-regulation of specific miRNAs could lead to an increased 'activation' that might contribute to the pathogenesis of HAL by increasing cell turnover and/or promotion of apoptosis.
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