Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation
Figure 2
Scheme for relationships between exercise-associated hemodynamic changes, inflammatory response, and Hsp. (a) Low or turbulent flow is associated with leukocyte extravasation [1] and expression of adhesion molecules [2], resulting in intimal hyperplasia, cell apoptosis [3] and inflammatory signaling [4]. The associated inflammatory signaling leads to increased oxidative stress, induction of inflammatory pathways such as c-Jun NH2-terminal kinase (JNK) [5] and NF-κB [6], and suppression of endothelial nitric oxide (eNOS) and oxidation of nitric oxide (NO) [7]. (b) In contrast, an exercise induced increase in laminar shear stress activates eNOS [1] and HSF1 [2]. HSF1 activation leads to increased heat shock proteins 25, 70, and 90 (Hsp25, Hsp70, and Hsp90) [3] which may inhibit many of these inflammatory processes indirectly via activation of eNOS signaling (Hsp90) [4] and directly through suppression of oxidative stress (Hsps 25, 70, and 90) [5] and inflammatory signaling including via the NF-κB pathway (Hsps 25 and 70) [6]. (c) Hsp may also directly reduce apoptosis (Hsps 70 and 90) [1] and hyperplasia (Hsp 70) [2]. Hsp70 has further been implicated in decreased expression of adhesion molecules [3] leading to a reduction of leukocyte extravasation [4] and expression of inflammatory cytokines [6]. Hsp70 also suppresses JNK signaling [5] 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.
