Abstract
Background:Vascular Smooth Muscle cells (VSMC) enact crucial roles in early vasculogenesis and sustenance of vascular integrity. However, aberrant proliferation of VSMC followed by migration into the blood vessel wall leads to the formation of vascular lesions accounting for the degeneration and remodelling of vascular basement membrane. In diabetes, hyperglycaemia accelerates VSMC proliferation and contributes to the initiation and progression of atherosclerotic lesions. Recently, acute glucose fluctuations have been implicated in the abnormal VSMC proliferation and complications of diabetic atherosclerosis. Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid (PUFA) has been shown to inhibit proliferation of several cell types implicating several different mechanisms. In the present study, we have investigated the effects of DHA on VSMC proliferation induced by stable and intermittent high glucose levels.Method:Confluent cultures of rat aortic VSMCs were treated with DHA for 24 hrs and then exposed to stable high glucose (25 mmol/L, SHG) or intermittent high glucose (5 mmol/L and 25 mmol/L alternating every 12 hrs, IHG) for 72 hrs. Cell proliferation was examined by the MTT viability assay, while apoptosis process was evaluated by the Hoechst staining, flow cytometry and caspase-3 activity assays.Results:Our data demonstrated that the hyper proliferation induced by stable and intermittent high glucose levels was significantly inhibited by the DHA pre-treatment. DHA significantly increased caspase-3 activity, resulting in enhanced DNA fragmentation and apoptosis.Conclusion:Our results suggest that DHA reduced the high glucose-induced proliferation of VSMC and induced cell apoptosis.
Highlights
Atheroscelerosis-associated macrovascular problems such as myocardial infarction and cerebrovascular diseases contribute to the major causes of morbidity and fatality in diabetic populations [1]
To test whether Docosahexaenoic acid (DHA) modifies IHG-induced proliferation of vascular smooth muscle cells (VSMCs), quiescent cultures were pretreated with DHA and exposed to constant or intermittent high glucose concentrations for 72 hrs
These results indicated that the VSMCs exposed to IHG showed increased cell proliferation than stable high glucose (SHG) and pretreatment with DHA significantly attenuated the induced proliferation in both SHG and IHG group
Summary
Atheroscelerosis-associated macrovascular problems such as myocardial infarction and cerebrovascular diseases contribute to the major causes of morbidity and fatality in diabetic populations [1]. Chronic hyperglycaemia has been recognised as the primary causal factor for macrovascular complications preceding to accelerated atherosclerosis in diabetes Both fasting and post prandial plasma sugar levels account for this process. A recent study on VSMCs found that IHG accelerated cell proliferation and is facilitated by enhanced osteopondin (OPN) synthesis, a cell adhesion molecule that can bind with the VSMCs surface integrin receptor, and mediate cellular adhesion, proliferation and migration [6]. These findings demonstrate that the inconstancies of glucose level contribute directly to the vascular complications in diabetic population. We have investigated the effects of DHA on VSMC proliferation induced by stable and intermittent high glucose levels
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