Relationship between the adipose-tissue hormone resistin and coronary artery disease
ABSTRACT Data on the cardiovascular risk associated with the adipose-tissue-related hormone resistin are scarce.
We measured serum resistin and established vascular risk factors in 547 consecutive patients (age 63+/-10 years) undergoing coronary angiography for the evaluation of stable coronary artery disease. Prospectively, we recorded major coronary events and cumulative vascular events over 4 years.
60% of our patients had significant coronary stenoses with a lumen narrowing > or =50%. Serum resistin was moderately but significantly correlated with age (r=0.139; p=0.001), high-sensitivity C-reactive protein (hsCRP; r=0.228; p<0.001) and decreasing renal function (r=0.240; p<0.001). However, there was no significant difference of serum resistin between patients with CAD and those in whom angiography did not show CAD (4.5 [3.1-5.8] vs. 4.3 [3.4-5.3] ng/ml; p=0.545) and between patients with > or =50% coronary narrowings and those without such lesions (4.5 [3.2-5.9] vs. 4.3 [3.1-5.5] ng/ml; p=0.265). Prospectively, Cox regression analyses neither indicated an association between serum resistin and major coronary events nor between serum resistin and cumulative vascular events.
Among coronary patients serum resistin is significantly correlated with hsCRP, age and decreasing renal function but resistin is neither associated with the presence of significant coronary stenoses nor with the incidence of future vascular events.
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Article: Resistin in Rodents and Humans[Show abstract] [Hide abstract]
ABSTRACT: Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.Diabetes & metabolism journal 12/2013; 37(6):404-414. DOI:10.4093/dmj.2013.37.6.404
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ABSTRACT: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10-1.64) and 1.99 (1.55-2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10-1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06-1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry.PLoS ONE 06/2013; 8(6):e64729. DOI:10.1371/journal.pone.0064729 · 3.53 Impact Factor
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ABSTRACT: Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10(-12)) and SNP rs13144478 (P = 6.19 × 10(-18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10(-7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.Human Molecular Genetics 07/2012; 21(21):4774-80. DOI:10.1093/hmg/dds300 · 6.68 Impact Factor