Abstract
Background: Apolipoprotein E4/E4 is the most significant risk factor known to cause Alzheimer dementia [1], but also crucial in atherogenesis as pathological correlative of coronary heart disease. The present investigation elucidates the role of IDLapoE isoforms in flow-dependent vascular reactivity. Methods: Isometric tension, membrane potential and cyclic nucleotide concentrations were measured in segments of human coronary arteries from heart transplantation. Results: The results of the mechanical recording are summarized in the Table. Upon a basal flow rate of 3 mL/min, the initial tension showed a graded course in normal preparations: cooled IDL (10 mg/dL) enhanced mechanical force (+0.8%), IDLapoE4/E4 (+9.5%) and IDLapoE0/E0 (from an apoE ‘knockout man’) (+19.1%) as compared to the controls in Krebs solution. Flow-dependent relaxation was impaired by 20% in apoE4/E4 solution, whereas apoE0/E0 caused a flow-dependent contraction by 85%. Endothelium-denuded segments had basically a higher tone on grounds of an impaired NO release. Membrane potentials reflected tension: hyperpolarization of the VSMCs preceded relaxation, depolarization preceded contraction. For the first time in literature, we report on a chemomechanical coupling curve. Conclusion: IDLapoE4/E4 impaired flow-dependent vasodilatation and was only exceeded in its deleterious effect by vasoconstrictive IDLapoE0/E0. There is growing evidence that binding of apoE4/E4 and apoE0/E0 to the flow sensor proteoheparan sulfate leads to nanoplaque build up [2] at the endothelium - blood interface and thus impairs vascular reactivity.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call