Changes in small heat shock proteins HSPB1, HSPB5 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats.

The mechanisms underlying mitochondrial impairment in the failing heart are not yet clearly defined. In the present study, we examined the involvement of changes in small heat shock proteins (HSPs) such as HSPB1, HSPB5 and HSPB8 in mitochondrial dysfunction of the failing heart. Hemodynamic parameters of rats with myocardial infarction at the 2nd and 8th weeks (2W- and 8W-) after coronary artery ligation (CAL) were measured. The 8W-CAL rats, but not the 2W-CAL ones, showed the signs of the chronic heart failure concomitant with a reduced mitochondrial oxygen consumption rate. In the mitochondrial fraction prepared from the heart of the 2W-CAL animals, the contents of small HSPs and phosphorylated small HSPs were increased, suggesting that these increases contributed to the preservation of the mitochondrial energy-producing ability. In the failing heart, HSPB1 and HSPB8 contents and phosphorylated small HSP contents in the mitochondrial fraction were decreased, suggesting that a reduction in mitochondrial translocation of these small HSPs led to impaired mitochondrial energy-producing ability. To further define the submitochondrial locations of these small HSPs, we performed mitochondrial subfractionation. The contents of small HSPs in the 2W-CAL rats were increased in the mitochondrial inner-membrane fraction, whereas those of the 8W-CAL rats were reversed to those of the control animals. These findings suggest that small HSPs, at least in part, play an important role in the development of the impaired mitochondrial energy-producing ability that leads to heart failure after a myocardial infarction.