Introduction:
Angiogenesis is the growth of new blood vessels. It begins in the womb and continues throughout life, in both health and disease, until old age. Capillaries (tiny blood vessels) are necessary for all tissues for the diffuse exchange of nutrients and metabolites. Alterations in metabolic activity lead to proportional changes in angiogenesis (formation of blood vessels) and, thus, in capillary action. Oxygen plays the main role in this regulation.
Hemodynamic factors are important for vascular network survival and structural adaptation of the vessel wall. The recognition that regulation of angiogenesis may have therapeutic value has generated considerable interest over the past 40 years. Stimulation of angiogenesis is useful in treating ischemic heart disease, peripheral artery disease, and wound healing. Reducing or inhibiting angiogenesis is useful in treating cancer, eye disease, rheumatoid arthritis (an autoimmune condition), and other diseases. Capillaries grow and recede within healthy tissue according to functional requirements. Exercise stimulates skeletal muscle and cardiac angiogenesis. Lack of exercise leads to capillary retraction. Capillaries grow within adipose tissue on gaining weight and shrink on losing weight. Angiogenesis occurs throughout a person’s life.
What Is Therapeutic Angiogenesis?
The ischemic disease is caused by reduced blood supply, leading to reduced oxygen transport and nutrient uptake, and is a leading cause of disability and death. Angiogenic therapy is central to the treatment of these diseases. Stem cells have been used in animal models and clinical studies to treat various ischemic diseases. Recently, the efficacy of stem cell therapy has increasingly been attributed to exocrine functions, especially extracellular vesicles. Extracellular vesicles are thought to function as intercellular communication vehicles that transport information molecules such as proteins, messenger ribonucleic acid (mRNA), microRNA, deoxyribonucleic acid (DNA) fragments, and lipids.
What Is the Role of Angiogenesis?
Angiogenesis is one of the most important processes in human physiology, and it plays a role in reproduction, fetal growth, wound healing, and tissue repair. This multi-step process is tightly controlled temporally by the 'on and off switch' mechanism between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis can lead to several angiogenic disorders, such as vascular insufficiency (myocardial ischemia or critical limb ischemia) and hyperproliferation of blood vessels (hemangiomas, neovascular tumors, retinopathy).
Thus, understanding angiogenesis and its subsequent successful manipulation can envision many therapeutic possibilities. Here, we examine the clinical significance of angiogenesis and discuss potential pro-and anti-angiogenic agents for treating cancer and other angiogenic diseases.
What Is the Process of Angiogenesis?
The process of angiogenesis is listed below:
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Angiogenic factors bind to receptors on endothelial cells and activate the signaling matrix metalloproteinases (proteins that cause the breakdown of extracellular matrix) are activated and degrade the extracellular matrix.
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Endothelial cells migrate from existing capillary walls and proliferate.
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Integrins are expressed by endothelial cells and promote their adhesion to the extracellular matrix and migration into tubule formation.
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Angiopoietin 1 binds to Tie-2 receptors and stimulates pericyte recruitment and vascular stabilization.
What Is the Role of Therapeutic Angiogenesis in Ischemic Heart Disease?
Angiogenic therapeutics that promote the angiogenic process are useful in treating angiogenesis-deficient diseases. Angiogenic agents can treat ischemic heart disease as an angiogenic therapeutic approach to repair and regenerate cardiac tissue. Treatment goals for this disease are to stimulate angiogenesis to improve blood flow, deliver survival factors to sites of tissue repair, recruit regenerative stem cell populations, and ultimately restore tissue morphology and function. Therapeutic angiogenesis has been shown to revascularize ischemic heart tissue, reduce the progression of tissue infarction, and avoid the need for invasive surgery and tissue/organ transplantation.
Although more than 2,000 heart patients have received some form of experimental angiogenic therapy, no Food and Drug Association (FDA) approved angiogenic drugs for treating ischemic cardiovascular disease are currently available. The first FDA-approved device to stimulate the growth of new blood vessels in diseased hearts is a laser used in a technique called direct myocardial revascularization (DMR) or trans myocardial revascularization (TMR).
What Is the Role of Stem Cell Therapy in Therapeutic Angiogenesis?
Over the past decade, stem cell transplantation, which induces angiogenesis to repair ischemic myocardium, has emerged as an innovative alternative to traditional methods of stimulating genes and proteins. In this technique, living cells are implanted into the myocardium, providing a regulated source of secreted growth factors and cytokines to reduce cardiomyocyte loss and improve the heart's vascular network.
Stem and progenitor cells possess beneficial properties such as self-renewal, high differentiation capacity, co-localization with vascular components, and proliferative capacity, making them ideal inducers or components of vascular growth. Stem and progenitor cells from diverse cell populations have shown therapeutic utility in promoting angiogenesis and restoring function in ischemic heart tissue.
The different cell types observed in such research studies include:
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Endothelial progenitor cells.
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Induced pluripotent stem cells (iPSC).
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Embryonic stem cells (ESC).
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Cardiac stem cells.
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Adipose-derived stem cells (ASC).
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Bone marrow mononuclear cells (BM-MNC).
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Bone marrow mesenchymal stem cells (BM-MSC).
What Are the Major Risks Associated With Angiogenic Agents?
The major risks associated with the use of therapeutic angiogenesis are listed below:
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Angiogenic agents are believed to have the potential to induce angiogenesis in a variety of tissues. This is important because, in clinical situations, it may not be possible to ensure that therapeutics are delivered only to the desired target tissue. An obvious potential complication is that angiogenic factors spread and induce unintended angiogenesis at adjacent and possibly distant sites.
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Another untoward consequence of angiogenic therapy is that the newly formed vessels can be functionally abnormal.
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The ability of angiogenic drugs to induce cell proliferation may have another significant side effect of promoting the growth of coexisting but undetected tumors.
Conclusion:
Angiogenesis is a term that means the new formation of blood vessels from pre-existing blood vessels. Angiogenic therapy deals with administering drugs from outside the body that promotes the growth of new blood vessels after birth. Angiogenesis can be induced for vascular repair in various human and animal models of inflammation, peripheral arterial disease, and ischemic heart disease. The complex nature of this process may cause adverse outcomes such as uncontrolled angiogenesis and the formation of leaky immature vessels. All currently tested angiogenic agents possess multiple potent biological activities that confer the ability to stimulate the growth of new blood vessels. But it is precisely these biological effects that can also lead to serious complications. It is hoped that strategies can be developed to deliver angiogenic drugs to target tissues with sufficient selectivity so that non-target tissues are not accidentally stimulated.
