Serum soluble receptor for advanced glycation end products (sRAGE) is independently associated with cigarette smoking in non-diabetic healthy subjects

Abstract

The receptor for advanced glycation end products (RAGE) is a cell surface receptor of immunoglobulin superfamily and is highly expressed in the lung tissue. 1 The lung tissue is directly exposed to cigarette smoke in smokers, and the cigarette smoke has been shown to elevate RAGE expression in cultured cells and in the lung tissues of animals. 2 Some of the diseases prevalent among cigarette smokers, particularly atherosclerotic cardiovascular diseases and cancer, have also been shown to be linked with RAGE signalling. 3 A soluble form of RAGE (sRAGE), which is a splice variant of full-length RAGE or a shedding/cleavage product of membrane-bound RAGE, has been found circulating in the plasma. The sRAGE has been considered to be protective against diseases originating from RAGE activation since sRAGE can bind and sequester RAGE ligands, and thereby, can reduce RAGE activation. 3 On the contrary, a pro-inflammatory role of sRAGE has also been described. 4,5 We therefore asked in the present study, whether sRAGE level is altered in cigarette smokers and is associated with smoking habit in non-diabetic healthy subjects.A total of 98 non-diabetic, otherwise healthy, male subjects were recruited from the employees of the Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, after giving written consent. The study was conducted according to the Declaration of Helsinki and was approved by the institutional ethical review committee. A fasting blood sample and medical history including detail history of cigarette smoking were collected. Subjects who reported AbstractThis study was designed to explore the relationship between serum levels of soluble receptor for advanced glycation end products (sRAGE) and cigarette smoking in non-diabetic healthy subjects. A total of 98 non-diabetic, otherwise healthy male subjects were recruited. A fasting blood sample and medical history including detail history of cigarette smoking was collected. The serum sRAGE levels were found significantly higher (p=0.002) in cigarette smokers (1475±422 pg/ml, n=45) compared with non-smokers (1165±350 pg/ml, n=53). Moreover, among the cigarette smokers, serum sRAGE levels were found significantly correlated with number of cigarettes smoked per day (r=0.60, p<0.001). In bivariate analysis in the total population, sRAGE positively correlated with smoking habit (r=0.37, p=0.002) and negatively correlated with systolic (r=-0.32, p=0.01) and diastolic blood pressure (r=-0.36, p=0.003). However, in stepwise multivariate linear regression model, sRAGE showed a significant independent association with smoking habit (b=0.32, p=0.007, R 2 =0.23).In conclusion, this study for the first time shows a significant elevation of serum sRAGE in cigarette smokers compared with non-smokers, a strong correlation between sRAGE and number of cigarettes smoked per day and an independent association of sRAGE with smoking habit in non-diabetic healthy subjects.

Periodontal Inflammatory Conditions Among Smokers and Never‐Smokers With and Without Type 2 Diabetes Mellitus

“…The present study is based on the hypothesis that periodontal inflammatory conditions are worse among smokers with T2DM than never‐smokers with T2DM. This was mainly speculated because both hyperglycemia and habitual smoking enhance the formation and accumulation of AGEs in the periodontal tissues, which jeopardize periodontal health 9,16 . Interestingly, in the present study, clinical and radiologic parameters of periodontal inflammation (PI, BOP, PD ≥4 mm, AL, and MBL) were comparable among smokers and never‐smokers with T2DM.…”

“…The deleterious effects of tobacco smoking on oral and systemic health are well documented 11‐15 . Habitual tobacco smoking has also been associated with an increased expression of receptors of AGEs in the gingival tissues 16 . This in turn jeopardizes the chemotactic and phagocytic functions of polymorphonuclear leukocytes and provokes a pro‐inflammatory effect by stimulating the secretion of cytokines and reactive oxygen species that directly cause breakdown of periodontal tissues 17‐20 .…”

Comparison of Periodontal Parameters and Self‐Perceived Oral Symptoms Among Cigarette Smokers, Individuals Vaping Electronic Cigarettes, and Never‐Smokers

“…Previous studies 18‐20 have also confirmed that CSs exhibit significantly greater number of sites with plaque accumulation, clinical AL, and PD ≥4 mm compared with NSs. One explanation in this context is that tobacco smoking is associated with increased expression of AGEs and their receptors in gingival tissues, which exacerbate oxidative stress and inflammatory responses 21 . BOP (a classic marker of periodontal disease severity 22 ) was masked among individuals in groups 1 and 2 compared with those in group 3.…”

Soluble form of receptor for advanced glycation end-products (sRAGE): do sRAGE ligands or anti-sRAGE auto-antibodies interfere with sRAGE quantification?

“…[47][48][49] Among these various factors, age, RAGE polymorphisms, smoking body-mass index and ethnicity could well play an important role in varying sRAGE levels. [49][50][51][52] Furthermore, strong evidence suggests a role of kidney dysfunction in increased sRAGE levels, although the specific mechanisms are unclear. 19,20,53 Compared to healthy young individuals, significantly higher sRAGE levels have been reported in healthy centenarians, 54 and a difference of around 500 pg/mL sRAGE has been associated with Gly82Ser polymorphism.…”