REGIONAL DISTRIBUTION OF HSP70 PROTEINS AFTER MYOCARDIAL-INFARCTION

Hypoxia and altered hemodynamic status, both components of myocardial infarction, have been shown to be potent inducers of the 70 kD family of heat shock proteins (HSP70). We hypothesized that after infarction, the surviving myocardium would synthesize HSP70 proteins in a tempora lly and regionally distinct pattern. We believed that there would be a lack of an HSP70 response in the infarcted area (I), reflecting the l oss of viable cells. We further postulated that tissues bordering infa rctions (M) would have a compromised HSP70 response. Conversely, we pr oposed that HSP70 would be induced in septal tissues (S) of the infarc ted heart, as a hypertrophic adaptation. A rat model of myocardial inf arction was used to examine the changes in relative concentration and distribution of three major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and endoplasmic reticular GRP78 (glucose regulate d protein) during 21 days of recovery. While all three HSP70 family pr oteins investigated were detected in all hearts from all groups at all time periods, experimental treatment (infarction) induced changes in relative protein concentrations that varied with time and sample site location. Relative concentrations of HSP72 and GRP78 were unchanged in the 24 h following infarction while relative HSP75 concentrations wer e halved in M tissues during the same time period. Between days 5 and 7, several changes were noted. M samples displayed nearly twice the re lative concentrations of HSP75 and GRP78 after infarction, but showed no change in HSP72. S tissues showed two-fold or larger increases in a ll three HSP70 family proteins. I samples showed unanticipated increas es in HSP75 and GRP78 during this time period. After 14 to 21 days of recovery, HSP70 family protein concentration levels in M, S, and I tis sues from infarcted hearts had returned to levels similar to those see n in control animals. We conclude that the myocardium is unable to, or does not, mount an immediate HSP70 response after infarction but does recover such activity by 5 - 7 days after infarction.