Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease

Abstract

Currently, atherosclerosis, which affects the vascular bed of all vital organs and tissues, is considered as a leading cause of death. Most commonly, atherosclerosis involves coronary and peripheral arteries, which results in acute (e.g., myocardial infarction, lower extremities ischemia) or chronic (persistent ischemia leading to severe heart failure) consequences. All of them have a marked unfavorable impact on the quality of life and are associated with increased mortality and morbidity in human populations. Lower extremity artery disease (LEAD, also defined as peripheral artery disease, PAD) refers to atherosclerotic occlusive disease of the lower extremities, where partial or complete obstruction of peripheral arteries is observed. Decreased perfusion can result in ischemic pain, non-healing wounds, and ischemic ulcers, and significantly reduce the quality of life. However, the progressive atherosclerotic changes cause stimulation of tissue response processes, like vessel wall remodeling and neovascularization. These mechanisms of adapting the vascular network to pathological conditions seem to play a key role in reducing the impact of the changes limiting the flow of blood. Neovascularization as a response to ischemia induces sprouting and expansion of the endothelium to repair and grow the vessels of the circulatory system. Neovascularization consists of three different biological processes: vasculogenesis, angiogenesis, and arteriogenesis. Both molecular and environmental factors that may affect the process of development and growth of blood vessels were analyzed. Particular attention was paid to the changes taking place during LEAD. It is important to consider the molecular mechanisms underpinning vessel growth. These mechanisms will also be examined in the context of diseases commonly affecting blood vessel function, or those treatable in part by manipulation of angiogenesis. Furthermore, it may be possible to induce the process of blood vessel development and growth to treat peripheral vascular disease and wound healing. Reactive oxygen species (ROS) play an important role in regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. With regard to the repair processes taking place during diseases such as LEAD, prospective therapeutic methods have been described that could significantly improve the treatment of vessel diseases in the future. Summarizing, regenerative medicine holds the potential to transform the therapeutic methods in heart and vessel diseases treatment.

In Vitro and In Vivo Characterization Methods for Evaluation of Modern Wound Dressings

“…Recent studies indicated a diabetic foot ulcers prevalence of 11.6% while venous and pressure ulcers affect 1–3% of the total population which are expected to rise in tandem with the aging population, low body mass index, and prolonged illness [ 34 , 35 ]. Arterial ulcers or peripheral artery disease (PAD) are associated with the occlusion of lower limb arteries, and advanced atherosclerosis (calcification and stenosis) and cause critical limb ischemia, tissue necrosis, and persistent inflammation [ 36 ]. The severity of chronic conditions of PAD increases with metabolic disease prevalence and is correlated to inflammation (for example, C-reactive protein) and fibrosis (for example, galectin-3) biomarkers [ 37 , 38 ].…”

Expression Profile of Genes Encoding Proteins Involved in Regulation of Vasculature Development and Heart Muscle Morphogenesis—A Transcriptomic Approach Based on a Porcine Model

“…The heart is essential for life, but it has limited regenerative capacity in the adult and decreased extent of microvasculature can have serious and irreversible consequences like heart failure (HF). Given these factors, the whole complex process of neovascularization [14] taking place within the heart tissue is so crucial to understanding. Moreover, because the myocardium itself could serve as a source of treatment, via resident cardiac progenitor cells [15] therefore generation of new blood vessels for delivery oxygen and nutrients to newly created cells is necessary for proper cardiac function.…”

CNPY2 governs PDGF‑BB‑treated vascular smooth muscle cell proliferation, migration and phenotypic transformation via the Akt/mTOR/GSK‑3β signaling pathway

“…Atherosclerosis (AS) involves the coronary and peripheral arteries and can have consequences such as ischemia of the lower limbs and myocardium, or chronic heart failure ( 1 ). Atherothrombosis represents the terminal manifestation of this pathology.…”