Non-classical mechanisms of heart repair

Vasculogenesis was long considered to be a mechanism of blood vessel formation limited to the embryo, and not used in adult vascular repair. Similarly, myocardial proliferation was generally thought to cease in the adult. Yet there is an extensive older literature suggesting that blood might be a source of adult angioblasts and somewhat more recent data indicate that cardiomyocytes may proliferate. Only recently has the significance of this literature been recognized and the findings more closely investigated. It is now clear that bone marrow-cells move into the blood as angioblasts and contribute to vascular repair and neovascularization in the adult. Bone marrow cells can also move into the damaged myocardium, proliferate, and repair the damaged heart. This review will discuss data relevant to these non-classical mechanisms of heart repair, principally vascular repair, and some of the scientific history that led to modern thinking. Though the literature in this field is replete with examples of conclusions not warranted by the data, despite oft-exaggerated claims, the data do show that these non-classical mechanisms can contribute to cardiovascular maintenance and repair. What remains to be deciphered is the physiological importance of the mechanisms.