Physiological and Pathological Angiogenesis in the Adult Pulmonary Circulation

Abstract

Angiogenesis occurs during growth and physiological adaptation in many systemic organs, for example, exercise-induced skeletal and cardiac muscle hypertrophy, ovulation, and tissue repair. Disordered angiogenesis contributes to chronic inflammatory disease processes and to tumor growth and metastasis. Although it was previously thought that the adult pulmonary circulation was incapable of supporting new vessel growth, over that past 10 years new data have shown that angiogenesis within this circulation occurs both during physiological adaptive processes and as part of the pathogenic mechanisms of lung diseases. Here we review the expression of vascular growth factors in the adult lung, their essential role in pulmonary vascular homeostasis and the changes in their expression that occur in response to physiological challenges and in disease. We consider the evidence for adaptive neovascularization in the pulmonary circulation in response to alveolar hypoxia and during lung growth following pneumonectomy in the adult lung. In addition, we review the role of disordered angiogenesis in specific lung diseases including idiopathic pulmonary fibrosis, acute adult distress syndrome and both primary and metastatic tumors of the lung. Finally, we examine recent experimental data showing that therapeutic enhancement of pulmonary angiogenesis has the potential to treat lung diseases characterized by vessel loss.

The pathophysiological basis of chronic hypoxic pulmonary hypertension in the mouse: vasoconstrictor and structural mechanisms contribute equally

“…The increase in total capillary endothelial surface area in the hypoxic lung observed in these experiments suggests that capillary angiogenesis had taken place. We observed that the harmonic mean thickness of the gas‐exchange membrane (including both tissue and plasma components) was not significantly increased in the hypoxic mouse lung, which taken together with the increased surface area, suggests that the capillary and epithelial changes induced by hypoxia would have increased the membrane diffusing capacity for oxygen (Weibel, 1999; McLoughlin & Keane, 2011). Such an increase would be a beneficial adaptive advantage in a hypoxic environment, such as that at high altitude.…”

Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung

“…In the lung, microvascular endothelial cells proliferate approximately twice as fast as macroarterial endothelial cells (16) Moreover, PVEC-derived angiocrine signals might facilitate regenerative alveologenesis as shown in rats subjected to unilateral pneumonectomy (9). The increased capillary bed with accompanied growth of the alveolar epithelium could be an important contribution for adapting to hypoxia by increasing the diffusing capacity of the lung thanks to an expansion of the effective surface area of the alveolar gas exchange membrane (18). Thus the robust proliferation of PVECs observed in this study might play a beneficial role in the adaptive response to chronic hypoxia.…”

Ghrelin Decreases Angiogenesis, HIF-1α and VEGF Protein Levels in Chronic Hypoxia in Lung Tissue of Male Rats

“…Angiogenesis occurs in the pulmonary circulation during physiological adaptation and/or pathological mechanisms in lung disease. 26,27 Indeed, hypoxia is a condition of decreased O 2 levels that is seen in high altitudes and many respiratory diseases. 6 It can stimulate lung angiogenesis in adults, 26,28 through many factors or cytokines.…”