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Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic
M Papadaki1, S G Eskin, J Ruef
1Department of Chemical Engineering and Harvard-MIT Health Science and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Insights
Diabetes mellitus disrupts vascular homeostasis, increasing cardiovascular disease risk. Understanding how blood flow shear stress affects vascular cells is key to comprehending diabetes complications.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Molecular Mechanisms of Disease
Background:
- Diabetes mellitus exacerbates cardiovascular diseases through metabolic derangements.
- Hyperglycemia impairs vascular homeostasis, affecting endothelium-dependent relaxation and coagulation.
- Atherosclerosis often develops at sites of complex blood flow and shear stress.
Purpose of the Study:
- To review molecular mechanisms of shear stress signal transduction in vascular cells.
- To explore shear stress's role in vascular cell gene regulation.
- To highlight the significance of the hemodynamic environment in diabetes.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of signal transduction pathways.
- Examination of gene regulation by shear stress.
Main Results:
- Shear stress profoundly influences vascular cell function.
- Molecular pathways mediate cellular responses to hemodynamic forces.
- Gene expression is modulated by shear stress in vascular cells.
Conclusions:
- Understanding shear stress molecular mechanisms is crucial for diabetes research.
- The hemodynamic environment plays a vital role in diabetes-related vascular dysfunction.
- Further investigation into shear stress in diabetes may reveal new therapeutic targets.
Abstract:
Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.