Cardiac and endothelial profiles in diabetic subjects with periodontitis : interlink, intervention implications & underlying molecular mechanisms

Abstract

A two-way relationship has been established between diabetes mellitus (DM) and periodontal disease. DM dramatically accounts for increased severity of periodontitis, whereas periodontal infection/inflammation is closely associated with diabetic complications. The present study investigated the effects of periodontal disease and its intervention on cardiac function, endothelial profiles and levels of circulating biomarkers in diabetic subjects. The underlying molecular mechanisms involved were explored. The cross-sectional study on 115 type 2 DM (T2DM) subjects with different periodontal conditions showed that the microvascular complication(s) was significantly associated with clinical attachment loss, independent of glycemic control (Chapter III). Echocardiographic analysis on the same cohort provided the first evidence that periodontitis could increase the risk for the exacerbation of left ventricle systolic and diastolic functional abnormalities assessed by global longitudinal strain and tissue Doppler index E/e' ratio, respectively (Chapter IV). Next, a subgroup of 82 non-smoking T2DM subjects was further assessed for quantification of circulating progenitor cells (CPCs), in connection to endothelial function. Subjects with periodontitis exhibited a lower number of CPCs (CD34+ and CD133+ cells) than the counterparts, despite a non-significant correlation between periodontitis and flow-mediated dilation (Chapter V). The 6-month randomised clinical trial extended to investigate the effects of non-surgical periodontal treatment on cardiac function, in parallel with the counts of CPCs. 58 T2DM subjects with moderate to severe periodontitis were randomised into Treatment (N=29) and Control (N=29) groups. Notably, the observation on a significant decrease in E/e’ ratio and increased counts of CD133+ cells at the follow-up revealed that periodontal treatment could effectively improve myocardial diastolic function (Chapter VI). Moreover, peripheral blood endothelial progenitor cells (EPCs) were isolated from 11 subjects of the Treatment group and seven control subjects at baseline and 6-month follow-up. It was found that effective periodontal therapy resulted in a pronounced reduction of immuno-inflammatory responses in EPCs assessed by their IL-6 and IL-8 transcripts (Chapter VII). The in vitro study attempted to evaluate the expression profiles of atherosclerosis-related genes in human coronary artery endothelial cells (HCAECs) treated by P. gingivalis (ATCC 33277) and its lipopolysaccharides (LPS). The PCR array results showed that P. gingivalis and its LPS dramatically induced the expression of multi-genes related to cellular adhesion, apoptosis and thrombosis (e.g., SELE, BIRC3 and SERPINB2). In conclusion, the present study on the cohort of T2DM subjects indicates that i) the presence of diabetic microvascular complication(s) is positively correlated with periodontal destruction; ii) periodontitis is closely associated with myocardial dysfunction and depletion of CPCs, implying a possibly increased risk of cardiovascular events; iii) periodontal treatment improves cardiac function, increases the counts of CD133+ cells and favorably modulates the immuno-inflammatory response in EPCs, suggesting a potentially beneficial effect on cardiovascular health; iv) the periodontal pathogen P. gingivalis is likely involved in the development of atherosclerosis in HCAECs. Our findings enhance the current evidence and notion of effective management of diabetic patients for better oral/periodontal health and general wellbeing through multidisciplinary teamwork.