The Mechanism of Coronary Artery Calcification in Centrally Obese Non-Diabetic Men: Study on The Interaction of Leptin, Free Leptin Index, Adiponectin, hs-C Reactive Protein, Bone Morphogenetic Protein-2 and Matrix Gla Protein

Antonia Anna Lukito, Syakib Bakri, Peter Kabo, Andi Wijaya

Abstract


Background: The calcium in the artery was thought to be the result of the imbalance or dysregulation of the promoter and inhibitor cytokines influenced by various subclinical and clinical conditions. This study aimed to investigate the interaction between central obesity, as an early subclinical condition, also known as a chronic low grade inflammation condition and coronary artery calcium (CAC) in non-diabetic population including the underlying pathomechanisms of a CAC in the early stage of atherosclerosis.

Materials and Methods: This was a cross-sectional pathway analysis study enrolling 60 central obesity non-diabetic men that underwent coronary calcium score scan, anthropometrics and biomarker assays.

Results: There was a positive correlation between increasing free leptin index/adiponectin (FLI/A) ratio and CAC (r=0.297; p<0.05). There was a positive correlation between increasing FLI/A ratio and plasma high sensitive C-reactive protein (hs-CRP) (r=0.318; p<0.05). Plasma hs-CRP and bone morphogenetic protein-2 (BMP-2)-matrix gla protein (MGP) dysregulation were positively correlated (r=0.221; p<0.05) after adjusted to risk factors including insulin resistance, hypertension, age, and dyslipidemia.

Conclusion: The study found that one of the pathways involved in CAC in the centrally obese non-diabetic male is might be due to an increase of free leptin and decrease of adiponectin. The free leptin and adiponection ratio also increased hs-CRP, which partially correlated to the dysregulation of BMP-2 and MGP.

Keywords: coronary artery calcification, central obesity, adipokines, bone regulator protein, pathomechanism


Full Text:

PDF

References


Mazzini MJ, Schulze PC. Proatherogenic pathways leading to vascular calcification. Eur J Radiol. 2006; 57(3): 384-9, CrossRef.

Giachelli CM. Vascular calcification mechanisms. J Am Soc Nephrol. 2004; 15(12): 2959-64, CrossRef.

Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol. 2002; 39(4): 695-701, CrossRef.

Belovici MI, Pandele GI. Arterial media calcification in patients with type 2 diabetes mellitus. Rev Med Chir Soc Med Nat Iasi. 2008; 112(1): 21-34, article.

Wang Z, Nakayama T. Inflammation, a link between obesity and cardiovascular disease. Mediators Inflamm. 2010; 2010: 1-17, CrossRef.

Rajala MW, Scherer PE. Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003; 144(9): 3765-73, CrossRef.

Shao JS, Cheng SL, Sadhu J, Towler DA. Inflammation and the osteogenic regulation of vascular calcification. Hypertension. 2010; 55(3): 579-92, CrossRef.

Tieu BC, Lee C, Sun H, Lejeune W, Recinos A 3rd, Ju X, et al. An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice. J Clin Invest. 2009; 119(12): 3637-51, CrossRef.

Johnson RC, Leopold JA, Loscalzo J. Vascular calcification. Circ Res. 2006; 99(10): 1044-59, CrossRef.

Hattori Y, Nakano Y, Hattori S, Tomizawa A, Inukai K, Kasai K. High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-κB activation in vascular endothelial cells. FEBS Lett. 2008; 582(12): 1719-24, CrossRef.

Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol. 2008; 52(15): 1201-10, CrossRef.

Thomopoulos C, Papadopoulos DP, Papazachou O, Bratsas A, Massias S, Anastasiadis G, et al. Free leptin is associated with masked hypertension in nonobese subjects. Hypertension. 2009; 53(6): 965-972, CrossRef.

Schaab M, Kratzsch J. The soluble leptin receptor. Best Pract Res Clin Endocrinol Metab. 2015; 29(5): 661-70, CrossRef.

Inoue M, Maehata E, Yano M, Taniyama M, Suzuki S. Correlation between the adiponectin-leptin ratio and parameters of insulin resistance in patients with type 2 diabetes. Metabolism. 2005; 54(3): 281-6, CrossRef.

Inoue M, Yano M, Yamakado M, Maehata E, Suzuki S. Relationship between the adiponectin-leptin ratio and parameters of insulin resistance in subjects without hyperglycemia. Metabolism. 2006; 55(9): 1248-54, CrossRef.

Norata GD, Raselli S, Grigore L, Garlaschelli K, Dozio E, Magni P, et al. Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. Stroke. 2007; 38(10): 2844-6, CrossRef.

Schmermund A, Baumgart D, Görge G, Grönemeyer D, Seibel R, Bailey KR, et al. Measuring the effect of risk factors on coronary atherosclerosis: coronary calcium score versus angiographic disease severity. J Am Coll Cardiol. 1998; 31(6): 1267-73, CrossRef.

Li X, Yang HY, Giachelli CM. BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 2008; 199(2): 271-7, CrossRef.

Zebboudj AF, Imura M, Boström K. Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2. J Biol Chem. 2002; 277(6): 4388-94, CrossRef.

Raggi P, Shaw LJ, Berman DS, Callister TQ. Gender-based differences in the prognostic value of coronary calcification. J Womens Health (Larchmt). 2004; 13(3): 273-83, CrossRef.

Ogier V, Ziegler O, Méjean L, Nicolas JP, Stricker-Krongrad A. Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans. Int J Obes Relat Metab Disord. 2002; 26(4): 496-503, CrossRef.

Kaser S, Tatarczyk T, Stadlmayr A, Ciardi C, Ress C, Tschoner A, et al. Effect of obesity and insulin sensitivity on adiponectin isoform distribution. Eur J Clin Invest. 2008; 38(11): 827-34, CrossRef.

Maahs DM, Ogden LG, Kinney GL, Wadwa P, Snell-Bergeon JK, Dabelea D, et al. Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation. 2005; 111(6): 747-53, CrossRef.

Parhami F, Basseri B, Hwang J, Tintut Y, Demer LL. High-density lipoprotein regulates calcification of vascular cells. Circ Res. 2002; 91(7): 570-6, CrossRef.

Dubey L, Hesong Z. Role of leptin in atherogenesis. Exp Clin Cardiol. 2006; 11(4): 269-75, article.

Hajer GR, van Haeften TW, Visseren FLJ. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J. 2008; 29(24): 2959-71, CrossRef.

Ikeoka D, Mader JK, Pieber TR. Adipose tissue, inflammation and cardiovascular disease. Rev Assoc Med Bras. 2010; 56(1): 116-21, CrossRef.

Singh P, Hoffmann M, Wolk R, Shamsuzzaman ASM, Somers VK. Leptin induces C-reactive protein expression in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2007; 27(9): e302-7, CrossRef.

Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003; 107(5): 671-4, CrossRef.

Shao JS, Cai J, Towler DA. Molecular mechanisms of vascular calcification. Arterioscler Thromb Vasc Biol. 2006; 26(7): 1423-30, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v4i2.104

Indexed by:

                     

                    

                    


Cell and BioPharmaceutical Institute