Mechanotransduction in vascular physiology and atherogenesis Cornelia Hahn and Martin A. Schwartz review the role of mechanical forces in vascular development, physiology, and atherosclerosis. Blood flow is crucial for vascular development and regulation of vessel diameter in adults. It is also a key factor in atherosclerosis, which occurs mainly in regions of arteries with disturbed flow. Recent studies highlight the role of endothelial cells in responding to flow, and the mechanisms that contribute to atherosclerosis progression. Mechanical forces such as fluid shear stress and blood pressure regulate vascular development and physiology. Fluid shear stress acts on endothelial cells, while blood pressure exerts circumferential stretch on vascular smooth muscle cells. These forces influence vascular remodeling and function. In arteries, flow patterns can lead to chronic inflammation, which can progress to atherosclerosis in individuals with other risk factors. Atherosclerosis occurs in arteries where lesions contain lipids, leukocytes, and smooth muscle cells. These plaques can narrow arteries, reducing blood flow and causing symptoms such as angina or heart failure. They can also rupture, leading to thrombus formation and vessel occlusion, which can cause myocardial infarction or stroke. Mechanical forces regulate vascular physiology by modulating artery diameters to meet tissue demands. Endothelial cells respond to flow by producing substances that relax surrounding smooth muscle, while vascular smooth muscle cells respond to stretch by remodeling the vessel wall. Both cell types respond to mechanical forces to maintain vascular function. Potential mechanotransducers include ion channels, integrins, receptor tyrosine kinases, and primary cilia. The cytoskeleton plays a role in transmitting forces from the apical domain to the basal or lateral domains. Adhesion receptors such as PECAM-1 and VE-cadherin mediate responses to flow by activating signaling pathways that lead to cell responses. Luminal membrane proteins such as the glycocalyx may also mediate flow responses. Flow induces changes in membrane fluidity and activates G proteins, which can trigger signaling pathways. Mechanosensitive ion channels and ATP release are also involved in flow responses. Primary cilia in endothelial cells may contribute to sensing low shear stress in atherosclerosis-prone regions. These cilia are involved in flow-sensing and may mediate mechanotransduction. Blood flow patterns such as low flow, flow separation, and turbulence are associated with atherosclerosis. These disturbed flow patterns activate pro-inflammatory pathways, leading to endothelial cell activation, leukocyte recruitment, and plaque formation. Atheroprotective flow patterns such as high laminar shear reduce inflammation and promote endothelial cell function. These patterns activate anti-atherosclerotic pathways, while disturbed flow activates pro-atherosclerotic pathways. The time course of atherogenic events involves immediate responses to shear stress that lead to long-term plaque formation. Shear-dependent signaling pathways such as NF-κB, ROS,Mechanotransduction in vascular physiology and atherogenesis Cornelia Hahn and Martin A. Schwartz review the role of mechanical forces in vascular development, physiology, and atherosclerosis. Blood flow is crucial for vascular development and regulation of vessel diameter in adults. It is also a key factor in atherosclerosis, which occurs mainly in regions of arteries with disturbed flow. Recent studies highlight the role of endothelial cells in responding to flow, and the mechanisms that contribute to atherosclerosis progression. Mechanical forces such as fluid shear stress and blood pressure regulate vascular development and physiology. Fluid shear stress acts on endothelial cells, while blood pressure exerts circumferential stretch on vascular smooth muscle cells. These forces influence vascular remodeling and function. In arteries, flow patterns can lead to chronic inflammation, which can progress to atherosclerosis in individuals with other risk factors. Atherosclerosis occurs in arteries where lesions contain lipids, leukocytes, and smooth muscle cells. These plaques can narrow arteries, reducing blood flow and causing symptoms such as angina or heart failure. They can also rupture, leading to thrombus formation and vessel occlusion, which can cause myocardial infarction or stroke. Mechanical forces regulate vascular physiology by modulating artery diameters to meet tissue demands. Endothelial cells respond to flow by producing substances that relax surrounding smooth muscle, while vascular smooth muscle cells respond to stretch by remodeling the vessel wall. Both cell types respond to mechanical forces to maintain vascular function. Potential mechanotransducers include ion channels, integrins, receptor tyrosine kinases, and primary cilia. The cytoskeleton plays a role in transmitting forces from the apical domain to the basal or lateral domains. Adhesion receptors such as PECAM-1 and VE-cadherin mediate responses to flow by activating signaling pathways that lead to cell responses. Luminal membrane proteins such as the glycocalyx may also mediate flow responses. Flow induces changes in membrane fluidity and activates G proteins, which can trigger signaling pathways. Mechanosensitive ion channels and ATP release are also involved in flow responses. Primary cilia in endothelial cells may contribute to sensing low shear stress in atherosclerosis-prone regions. These cilia are involved in flow-sensing and may mediate mechanotransduction. Blood flow patterns such as low flow, flow separation, and turbulence are associated with atherosclerosis. These disturbed flow patterns activate pro-inflammatory pathways, leading to endothelial cell activation, leukocyte recruitment, and plaque formation. Atheroprotective flow patterns such as high laminar shear reduce inflammation and promote endothelial cell function. These patterns activate anti-atherosclerotic pathways, while disturbed flow activates pro-atherosclerotic pathways. The time course of atherogenic events involves immediate responses to shear stress that lead to long-term plaque formation. Shear-dependent signaling pathways such as NF-κB, ROS,