Adiponectin is inversely related to plasminogen activator inhibitor type 1 in patients with stable exertional angina

Hidetomo Maruyoshi; Sunao Kojima; Tohru Funahashi; Shinzo Miyamoto; Jun Hokamaki; Hirofumi Soejima; Tomohiro Sakamoto; Hiroaki Kawano; Michihiro Yoshimura; Akira Kitagawa; Yuji Matsuzawa; Hisao Ogawa

doi:10.1160/TH03-12-0731

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(05): 1026-1030
DOI: 10.1160/TH03-12-0731

Cell Signaling and Vessel Remodeling

Schattauer GmbH

Adiponectin is inversely related to plasminogen activator inhibitor type 1 in patients with stable exertional angina

Hidetomo Maruyoshi

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Sunao Kojima

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Tohru Funahashi

²Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan

,

Shinzo Miyamoto

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Jun Hokamaki

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hirofumi Soejima

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Tomohiro Sakamoto

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hiroaki Kawano

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Michihiro Yoshimura

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Akira Kitagawa

³Clinical Trial Management, Graduate School, International University of Health and Welfare, Tokyo, Japan

,

Yuji Matsuzawa

⁴Sumitomo Hospital, Osaka, Japan

,

Hisao Ogawa

¹Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

› Author Affiliations

Abstract

Summary

Adipose tissue is a secretory organ producing a variety of bioactive substances, such as adiponectin. Adiponectin has antiatherogenic properties while plasminogen activator inhibitor type 1 (PAI-1) is closely involved in the development of atherosclerosis. The relationship between adiponectin and PAI-1 in patients with coronary artery disease (CAD) has not been clarified. This study examined plasma levels of adiponectin and PAI-1 in 64 patients with stable exertional angina (SEA) and 65 patients with the chest pain syndrome (CPS). Plasma logadiponectin levels were significantly lower in patients with SEA (0.62±0.08 µg/dL) compared to those with CPS (0.86± 0.05 µg/dL) (p<0.0001). The plasma levels of log-PAI-1 were significantly higher in patients with SEA (1.23±0.18 ng/mL) compared to those with CPS (1.15±0.22 ng/mL) (p<0.05). Plasma log-adiponectin levels correlated negatively with diabetes mellitus (DM), body mass index (BMI), log-PAI-1 (r=−0.284, p<0.001), triglyceride (TG), and remnant-like particles cholesterol (RLP-C), and positively with high-density lipoprotein cholesterol (HDL-C) levels. Plasma levels of log-PAI-1 correlated positively with DM, BMI, TG and RLP-C levels, and negatively with HDL-C levels. Multiple logistic regression analysis identified sex, angina pectoris, and PAI-1 as independent determinants of hyperadiponectinemia (p<0.05). Adiponectin is inversely related to PAI-1. DM, BMI, TG, HDL-C, and RLP-C are common mediators between adiponectin and PAI-1, and treatment for common mediators may prevent the development of CAD by reducing PAI-1 and increasing adiponectin levels.

Keywords

Adiponectin - angina pectoris - fibrinolysis - plasminogen activator inhibitor type 1

Full Text

References

References
1 Wiecek A, Kokot F, Chudek J. et al. The adipose tissue - a novel endocrine organ of interest to the nephrologist. Nephrol Dial Transplant 2002; 17: 191-5.
2 Arita Y, Kihara S, Ouchi N. et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83.
3 Ouchi N, Kihara S, Arita Y. et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-KB signaling through a cAMP-dependent pathway. Circulation 2000; 102: 1296-301.
4 Ouchi N, Kihara S, Arita Y. et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473-6.
5 Okamoto Y, Arita Y, Nishida M. et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000; 32: 47-50.
6 Ouchi N, Kihara S, Arita Y. et al. Adipocytederived protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057-63.
7 Ouchi N, Kihara S, Funahashi T. et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107: 671-4.
8 Kojima S, Funahashi T, Sakamoto T. et al. The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart 2003; 89: 667-8.
9 Kumada M, Kihara S, Sumitsuji S. et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003; 23: 85-9.
10 Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000; 342: 1792-801.
11 Sakamoto T, Yasue H, Ogawa H. et al. Association of patency of the infarct-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction. Am J Cardiol 1992; 70: 271-6.
12 Masuda T, Yasue H, Ogawa H. et al. Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina. Am Heart J 1992; 124: 314-9.
13 Hamsten A, Wiman B, de Faire U. et al. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63.
14 Hamsten A, de Faire U, Walldius G. et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 02: 3-9.
15 Juhan-Vague I, Pyke SD, Alessi MC. et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996; 94: 2057-63.
16 Huber K, Resch I, Stefenelli T. et al. Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis. Thromb Haemost 1990; 63: 336-9.
17 Alessi MC, Peiretti F, Morange P. et al. Production of Plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-7.
18 Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-Arterioscler. Thromb Vasc Biol 1998; 18: 1-6.
19 Shimomura I, Funahashi T, Takahashi M. et al. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 1996; 02: 800-3.
20 Halleux CM, Takahashi M, Delporte ML. et al. Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 2001; 288: 1102-7.
21 Report of a WHO Study Group. Prevention of diabetes mellitus: World Health Organization. Geneva: 1994. World Health Organization. Tech. Rep. Ser., No. 844.
22 Ono T, Sogabe M, Ogura M. et al. Automated latex photometric immunoassay for total plasminogen activator inhibitor-1 in plasma. Clin Chem 2003; 49: 987-9.
23 Hotta K, Funahashi T, Arita Y. et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595-9.
24 Yamauchi T, Kamon J, Waki H. et al. The fatderived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 07: 941-6.
25 Okamoto Y, Kihara S, Ouchi N. et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106: 2767-70.
26 Declerck PJ, De Mol M, Vaughan DE. et al. Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a noninhibitory substrate for tissuetype plasminogen activator. J Biol Chem 1992; 15: 11693-6.