Abstract
A 3-minute ischemia/reperfusion caused expressions of angiogenic factors, bFGF and VEGF in 2 hours, PCNA in 24 to 96 hours in cardiac tissues, followed by an increase in capillaries in one month. X-ray (20 gray) exposure of rats also increased bFGF and VEGF, and capillary density in one month. A simple i.v. injection of bFGF or VEGF failed to cause any capillary increase. Thus, microdamages in cardiac tissues seemed necessary for the rapid increase in capillaries. Trials were made to elucidate the underlying mechanisms. In SHRSP the hypertrophy of cardiomyocytes exceeded the growth of capillaries, resulting in a low capillary density. Treatments of SHRSP using ACEI and/or angiotensin receptor blocker suppressed the hypertrophy in cardiomyocytes and increased the capillary density. Administration of clenbuterol to normal rats caused hypertrophy of cardiomyocytes accompanied with the reduction in the capillary density. The hypertrophy probably reduced the interstitial space among cardiomyocytes and suppressed the capillary proliferation. Expressions in bFGF and VEGF, and an increase in capillary density were found in 20 week-old OLETF rats (a model rat for type2 diabetes). However, an increase was found in PAI-1 expression in 40 to 60 week-old OLETF without any significant increase in capillary density. The expression of PAI-1 probably reduced the destruction rate in the extracellular matrix by plasmin, resulting in a retardation in the capillary proliferation. These data suggested that matrix destruction is required for the capillary proliferation and that the destruction may be accelerated by the 3 minute transient ischemia in cardiac tissues. [Jpn J Physiol 54 Suppl:S90 (2004)]
