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Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines.
Eur J Clin Invest 2005; 35(9):583-90EJ

Abstract

BACKGROUND

PAI-1, an important inhibitor of fibrinolysis, is increased in obese subjects and has been shown to be an independent risk factor for cardiovascular disease. In the present study, we investigated the association between circulating levels of PAI-1 and locally produced PAI-1 in adipose tissue and body fat distribution and adipokines (TNF-alpha, TNF receptors, IL-6, IL-8) in patients with and without HIV-associated lipodystrophy syndrome (HALS).

MATERIALS AND METHODS

Eighteen men with HALS and 18 men with HIV but without HALS were investigated. DEXA and computed tomography scan were performed to determine total body fat and visceral adipose tissue mass. Insulin sensitivity was determined by the euglycaemic clamp technique. Plasma levels of PAI-1 and cytokines were determined. In addition, PAI-1, TNF-alpha, IL-6 and IL-8 mRNA levels in subcutaneous adipose tissue were measured by real-time reverse transcriptase polymerase chain reaction.

RESULTS

HALS patients were characterized by a 3-fold increased visceral adipose tissue (P < 0.001) and reduced limb fat (P < 0.01) as compared with non-HALS patients but with no difference in total fat mass between the groups. Plasma PAI-1 was increased in HALS patients (16.7 ng mL(-1) vs. 8.2 ng mL(-1), P < 0.05). Plasma PAI-1 was positively correlated with BMI (r = 0.74, P < 0.01), plasma TNF-alpha level (r = 0.64, P < 0.01), sTNFR-I (r = 0.38, P < 0.05), and visceral fat (r = 0.67, P < 0.01). Moreover, plasma PAI-1 was negatively associated with insulin sensitivity (r = -0.57, P < 0.01) and the percentage of limb fat (r = -0.57, P < 0.01). A positive correlation was found between plasma PAI-1 and TNF-alpha mRNA level. No association was, however, found between plasma PAI-1 and PAI-1 mRNA level in adipose tissue.

CONCLUSION

Plasma PAI-1 is increased in HALS patients and it is suggested that dysregulation of the TNF-system (high TNFalpha and high sTNFR1) may play a role in up-regulating PAI-1 in HALS.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16128865

Citation

He, G, et al. "Plasminogen Activator Inhibitor Type 1 (PAI-1) in Plasma and Adipose Tissue in HIV-associated Lipodystrophy Syndrome. Implications of Adipokines." European Journal of Clinical Investigation, vol. 35, no. 9, 2005, pp. 583-90.
He G, Andersen O, Haugaard SB, et al. Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines. Eur J Clin Invest. 2005;35(9):583-90.
He, G., Andersen, O., Haugaard, S. B., Lihn, A. S., Pedersen, S. B., Madsbad, S., & Richelsen, B. (2005). Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines. European Journal of Clinical Investigation, 35(9), pp. 583-90.
He G, et al. Plasminogen Activator Inhibitor Type 1 (PAI-1) in Plasma and Adipose Tissue in HIV-associated Lipodystrophy Syndrome. Implications of Adipokines. Eur J Clin Invest. 2005;35(9):583-90. PubMed PMID: 16128865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines. AU - He,G, AU - Andersen,O, AU - Haugaard,S B, AU - Lihn,A S, AU - Pedersen,S B, AU - Madsbad,S, AU - Richelsen,B, PY - 2005/9/1/pubmed PY - 2005/12/20/medline PY - 2005/9/1/entrez SP - 583 EP - 90 JF - European journal of clinical investigation JO - Eur. J. Clin. Invest. VL - 35 IS - 9 N2 - BACKGROUND: PAI-1, an important inhibitor of fibrinolysis, is increased in obese subjects and has been shown to be an independent risk factor for cardiovascular disease. In the present study, we investigated the association between circulating levels of PAI-1 and locally produced PAI-1 in adipose tissue and body fat distribution and adipokines (TNF-alpha, TNF receptors, IL-6, IL-8) in patients with and without HIV-associated lipodystrophy syndrome (HALS). MATERIALS AND METHODS: Eighteen men with HALS and 18 men with HIV but without HALS were investigated. DEXA and computed tomography scan were performed to determine total body fat and visceral adipose tissue mass. Insulin sensitivity was determined by the euglycaemic clamp technique. Plasma levels of PAI-1 and cytokines were determined. In addition, PAI-1, TNF-alpha, IL-6 and IL-8 mRNA levels in subcutaneous adipose tissue were measured by real-time reverse transcriptase polymerase chain reaction. RESULTS: HALS patients were characterized by a 3-fold increased visceral adipose tissue (P < 0.001) and reduced limb fat (P < 0.01) as compared with non-HALS patients but with no difference in total fat mass between the groups. Plasma PAI-1 was increased in HALS patients (16.7 ng mL(-1) vs. 8.2 ng mL(-1), P < 0.05). Plasma PAI-1 was positively correlated with BMI (r = 0.74, P < 0.01), plasma TNF-alpha level (r = 0.64, P < 0.01), sTNFR-I (r = 0.38, P < 0.05), and visceral fat (r = 0.67, P < 0.01). Moreover, plasma PAI-1 was negatively associated with insulin sensitivity (r = -0.57, P < 0.01) and the percentage of limb fat (r = -0.57, P < 0.01). A positive correlation was found between plasma PAI-1 and TNF-alpha mRNA level. No association was, however, found between plasma PAI-1 and PAI-1 mRNA level in adipose tissue. CONCLUSION: Plasma PAI-1 is increased in HALS patients and it is suggested that dysregulation of the TNF-system (high TNFalpha and high sTNFR1) may play a role in up-regulating PAI-1 in HALS. SN - 0014-2972 UR - https://www.unboundmedicine.com/medline/citation/16128865/Plasminogen_activator_inhibitor_type_1__PAI_1__in_plasma_and_adipose_tissue_in_HIV_associated_lipodystrophy_syndrome__Implications_of_adipokines_ L2 - https://doi.org/10.1111/j.1365-2362.2005.01547.x DB - PRIME DP - Unbound Medicine ER -