research-article

Pavel Igorevich Makarevich1, 2, 3∗ and Yelena Viktorovna Parfyonova1, 3
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Abstract

Angiogenesis as therapeutic target has emerged since early works by Judah Folkman, yet his “holy grail” was inhibiting vascular growth to block tumor nutrition. However, in modern biomedicine, “therapeutic angiogenesis” became a large field focusing on stimulation of blood vessel growth for ischemia relief to reduce its detrimental effects in the tissues. In this review, we introduce basic principles of tissue vascularization in response to ischemia exploited in this field. An overview of recent status in therapeutic angiogenesis is given with introduction to emerging technologies, including gene therapy, genetic modification of cells ex vivo and tissue engineering.
Keywords: therapeutic angiogenesis, growth factors, cytokines, gene therapy, cell therapy, plasmid, viral vector

1. Introduction

Blood vessel growth is a natural process driven by multiple stimuli of which hypoxia is one of the strongest inducing potent response until O2 pressure is normalized by the blood coming through de novo formed vasculature. However, a large group of diseases is caused by hypoxic or ischemic state of tissue. These include peripheral artery disease (PAD) and intermittent claudication (IC), coronary heart disease (CHD), myocardial infarction (MI) and ischemic stroke. Accompanied by endothelial dysfunction and age-related reduction of angiogenic response, they result in disabilities and mortality rate of 25–25% annually. Existing strategies for surgical bypass or endovascular interventions have limited efficacy as far as a cohort of non-option patients expands reaching 25–50% after certain extent of disease progression. Moreover, long-term prognosis after most interventions is negative as grafts undergo restenosis and vascular biocompatible prosthetics are yet to come for wide application. This drew attention of physicians and researchers to the concept of angiogenic therapy to stimulate body’s own resource and form new blood vessels to relieve ischemia. During recent decade the field of biomedicine known as therapeutic angiogenesis evolved rapidly using protein delivery, gene therapy, cell therapy and tissue engineering for induction of vessel growth and overview of its basic concepts and recent achievements will be presented to the reader in chapters below.