Unorthodox angiogenesis in skeletal muscle

Area of Science:

• Physiology
• Cell Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new capillaries, is crucial for skeletal muscle adaptation.
• Existing models of capillary growth are largely based on developmental, pathological, or in vitro studies.
• The specific mechanisms of angiogenesis in mature skeletal muscle under physiological conditions are not fully understood.

Purpose of the Study:

• To investigate the morphological patterns of angiogenesis in adult skeletal muscle.
• To determine if capillary neoformation follows established temporal paradigms.
• To elucidate how mechanical stimuli influence the pattern of skeletal muscle angiogenesis.

Main Methods:

• Adult rats were subjected to increased blood flow (prazosin), muscle overload (surgical removal), or chronic electrical stimulation.
• Extensor muscles were collected at intervals for electron microscopy.
• Capillary ultrastructure and endothelial cell (EC) proliferation (BrdU labeling) were systematically examined.

Main Results:

• Increased blood flow induced capillary growth via luminal division without sprouting.
• Muscle stretch promoted EC proliferation and abluminal sprouting, with basement membrane (BM) loss at sprout tips.
• Chronically stimulated muscles exhibited both growth mechanisms, indicating additive effects.

Conclusions:

• Physiological angiogenesis in adult skeletal muscle utilizes mechanisms distinct from those observed in development or pathology.
• The pattern of capillary growth is dictated by the mechanical stimulus's polarity: intra-luminal shear stress or abluminal stretch.
• Endothelial cell proliferation precedes observable angiogenesis in response to mechanical stimuli.