Aim: 

The ShcA gene encoding for p66Shc, p52Shc and p46Shc isoforms is crucial for heart development and function. Targeted deletion of the p66Shc is beneficial during acute ischemia/ reperfusion injury. The possible role of p66Shc in postinfarction remodeling is not known. Aim was to investigate if p66Shc gene deletion influences heart remodeling.

Methods: 

Myocardial infarction was induced in vivo by left coronary artery occlusion in C57Bl6 male mice, either wild types (WT) or p66Shc knockouts (p66KO). Cardiac expression of p66Shc was evaluated serially postinfarction in WT by immunoblotting (n=70). Heart function of WT and p66KO was assessed by echocardiography and pressure-volume loops 6 weeks post-infarction (n=19 per group). Hearts from WT and p66KO were harvested 3 days postinfarction for evaluation of infarct size (LillieÕs trichrome), mRNA level for collagen type Ia1 (real time PCR) and gelatinases-A,B activity (gel zymography) compared with uninfarcted (n=5 per group).

Results: 

Cardiac p66Shc expression increased starting one week post-infarction (p< 0, 001). p66KO had improved early survival -84% vs. 43% (p< 0, 01). Heart rupture caused death in 16% of p66KO and 63% in WT (p< 0.05). Heart function was similarly impaired in both groups after 6 weeks, although p66KO had less left ventricular dilatation (p< 0, 01). Infarct size did not differ between groups three days post-infarction. mRNA expression for collagen type Ia1 was increased (p< 0, 05) and pro-gelatinase-A was down-regulated (p< 0, 01) in p66KO post-infarction.

Conclusion: 

The p66Shc isoform plays a detrimental role during early post-infarction remodeling. Its deletion decreased the incidence of heart rupture, possibly due to modulation of collagen turnover.