{'fraction_non_alphanumeric': 0.023650156180276664, 'fraction_numerical': 0.005800981704596163, 'mean_word_length': 6.094936708860759, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Small molecule approaches for promoting ischemic tissue vascularization.

See related article, pages 257–265 

Angiogenesis and arteriogenesis identify 2 specific processes that lead to the formation of new capillaries and the development of collateral vessels from pre-existing arterioles, respectively. Both processes characterize tissue repair and remodeling occurring in acute and chronic ischemic vascular diseases, and both processes represent the final targets of therapeutic angiogenesis aimed at providing an alternative treatment strategy for patients with lower limb ischemia and coronary artery disease.1,2

Angiogenesis and arteriogenesis are driven by distinct, but partially overlapping, cellular and molecular pathways. Whereas the role of hypoxia and angiogenic inducers seems to be the trigger for pathological angiogenesis (ie, tumors, inflammatory chronic diseases, retinal maculopathy), fluid shear stress might be the most important stimulus for initiation of arteriogenesis.1,2 Besides these specific initial triggers, angiogenesis and arteriogenesis share growth factors, chemokines, proteases, inflammatory cells, and bone marrow-derived cells, which play quantitatively different roles in sustaining and refining these mechanisms of vascularization. A paradigmatic example of these differences is the differing roles played by inflammatory cells in angiogenesis and arteriogenesis. In fact, angiogenesis may also occur in the absence of leukocyte recruitment. On the contrary, fluid shear stress activates the expression of multiple genes in endothelial cells (EC) aimed mainly to trigger the attraction and adhesion of circulating blood cells, which are necessary and sufficient functions to maintain arteriogenesis.

In the last 10 years, relevant strides have been made with respect to therapeutic angiogenesis. Proof-of-concept evidence for therapeutic growth factor, both gene and protein-mediated neovascularization, was provided in animal models of chronic myocardial and hindlimb ischemia. After encouraging results in human phase I trials using the prototypical growth factor families (vascular endothelial growth factors [VEGFs] and fibroblast growth factors [FGFs]), large randomized placebo-controlled …