Fluid Shear Stress Induces Heat Shock Protein 60 Expression in Endothelial Cells In Vitro and In Vivo

Abstract

Abstract-Recent investigations indicate that the initial event in the pathogenesis of atherosclerosis involves an (auto)immunologic injury to the vessel wall. Heat shock proteins (hsps), which are expressed on the endothelial cell surface, constitute possible autoantigens. After being exposed to shear stress of 30 dyne/cm 2 in vitro by means of a rotational viscometer, human umbilical vein endothelial cells were immunohistochemically stained for hsp 60 by the monoclonal antibody ML-30; static control cells were negative. Maximal hsp 60 induction was observed after 12 hours of hemodynamic stress. In Northern blots, the level of hsp 60 mRNA was markedly increased after only 1 hour of shear stress in human umbilical vein endothelial cells compared with static control cells. In vivo investigations in Lewis rats confirmed these in vitro findings: the intima and media of frozen sections of the right common carotid artery exposed to increased wall shear stress (after ligation of the left common carotid artery) were stained for hsp 60. The vessel wall of the left low-shear-stress-exposed side was negative. These findings demonstrate that shear stress results in hsp 60 induction in endothelial cells in vivo and in vitro, providing the prerequisite for humoral and cellular reactions to endothelial hsp in the earliest stages of atherosclerosis.

Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events

“…According to the hypothesis of Wick et al, 23 the association between high levels of anti-hsp65 antibodies and atherosclerotic vascular diseases is attributable to an autoimmune reaction to endothelial cells that express high levels of hsp60 due to stress, such as oxidized LDL, free radicals, local infections, cytokines, or hemodynamic stress. 24 In a separate analysis of 3168 patients from HOPE, high baseline plasma fibrinogen and high serum concentration of IgG antibodies against CMV were independent predictors of cardiovascular events. High serum anti-hsp65 antibody levels were associated with 2.1-fold risk (present study), whereas high fibrinogen levels were associated with 1.4-fold risk for development of new myocardial infarction, stroke, or cardiovascular death (Smieja et al, unpublished data, 2002).…”

Association of autoantibodies to heat‐shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies

“…Arterial thrombi tend to occur at sites of arterial plaque rupture where shear stress is high, while venous thrombi tend to occur at sites where the vessel wall is often normal and blood flow and shear stress are low (33). Elevated shear stress, which occurs more frequently in arterial than in venous beds, can result in endothelial surface expression of Hsp60 both in vitro and in vivo (34). Increased expression of Hsp60 in arterial vessels may explain the association of anti-Hsp60 with arterial but not venous thrombovascular events.…”

“…The association of anti-Hsp60 with arterial vascular events but not venous vascular events suggests that Hsp60 is expressed in the arterial bed but not the venous bed. Elevated shear stress, which occurs more frequently in arterial than in venous beds, can result in endothelial surface expression of Hsp60 both in vitro and in vivo (34). Differential endothelial cell expression of Hsp60 may at least partially explain the greater susceptibility of the arterial bed to antiHsp60.…”

Joint Effects of Antibody to Heat Shock Protein 60, Hypertension, and Diabetes on Risk of Coronary Heart Disease in Chinese

“…High shear stress or increased blood pressure has been demonstrated to induce Hsp expression in endothelial cells or vascular smooth muscle cells (29,30 ). Enhanced expression of Hsp70 has been detected in hypertensive experimental animals (31,32 ).…”