Is physiological angiogenesis in skeletal muscle regulated by changes in microcirculation?

Area of Science:

• Physiology
• Microcirculation
• Angiogenesis

Background:

• Physiological angiogenesis occurs in various tissues, including reproductive organs, growing antlers, and active skeletal/cardiac muscles.
• Increased blood flow, velocity, pressure, and hematocrit are common factors in these conditions.
• Mechanical forces like shear stress and wall tension may disturb the endothelium, initiating angiogenesis.

Discussion:

• Microcirculation in skeletal muscles was studied under conditions of increased activity, blood flow, hematocrit, and mechanical stretch.
• Capillary growth occurred with increased activity, blood flow, and stretch, but not with increased hematocrit alone.
• Capillary proliferation was observed with electrical stimulation but not with increased blood flow alone.

Key Insights:

• Chronic electrical stimulation increased capillary diameter, arteriolar widening, capillary hematocrit, and red blood cell velocity, leading to higher shear stress and wall tension.
• Increased blood flow (via vasodilators) elevated shear stress but did not alter vessel diameters.
• Mechanical stretch of muscles also induced angiogenesis, suggesting a role for extravascular factors.

Outlook:

• Increased shear stress, wall tension, or mechanical stretch may initiate angiogenesis by endothelial cell damage or growth factor release.
• Endothelial cell-stimulating angiogenic factor (ESAF) levels increased in stimulated and stretched muscles.
• Prostaglandins and nitric oxide are involved in mediating capillary proliferation, as evidenced by reduced bromodeoxyuridine incorporation after inhibition.