Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation
Scheme for relationships between exercise-associated hemodynamic changes, inflammatory response, and Hsp. (a) Low or turbulent flow is associated with leukocyte extravasation  and expression of adhesion molecules , resulting in intimal hyperplasia, cell apoptosis  and inflammatory signaling . The associated inflammatory signaling leads to increased oxidative stress, induction of inflammatory pathways such as c-Jun NH2-terminal kinase (JNK)  and NF-κB , and suppression of endothelial nitric oxide (eNOS) and oxidation of nitric oxide (NO) . (b) In contrast, an exercise induced increase in laminar shear stress activates eNOS  and HSF1 . HSF1 activation leads to increased heat shock proteins 25, 70, and 90 (Hsp25, Hsp70, and Hsp90)  which may inhibit many of these inflammatory processes indirectly via activation of eNOS signaling (Hsp90)  and directly through suppression of oxidative stress (Hsps 25, 70, and 90)  and inflammatory signaling including via the NF-κB pathway (Hsps 25 and 70) . (c) Hsp may also directly reduce apoptosis (Hsps 70 and 90)  and hyperplasia (Hsp 70) . Hsp70 has further been implicated in decreased expression of adhesion molecules  leading to a reduction of leukocyte extravasation  and expression of inflammatory cytokines . Hsp70 also suppresses JNK signaling  further inhibiting inflammatory signaling and cytokine release. See text for a more complete description. — represents activating role; |— represents inhibitory role; - - - -: Hsp90 effects; ——: Hsp70 effects; -·-·-·-·: Hsp25 effects.