Abstract
Cardiovascular diseases are the leading cause of mortality worldwide. Such a widespread diffusion makes the conditions affecting the heart and blood vessels a primary medical and economic burden. It, therefore, becomes mandatory to identify effective treatments that can alleviate this global problem. Among the different solutions brought to the attention of the medical-scientific community, therapeutic angiogenesis is one of the most promising. However, this approach, which aims to treat cardiovascular diseases by generating new blood vessels in ischemic tissues, has so far led to inadequate results due to several issues. In this perspective, we will discuss cutting-edge approaches and future perspectives to alleviate the potentially lethal impact of cardiovascular diseases. We will focus on the consolidated role of resident endothelial progenitor cells, particularly endothelial colony forming cells, as suitable candidates for cell-based therapy demonstrating the importance of targeting intracellular Ca2+ signaling to boost their regenerative outcome. Moreover, we will elucidate the advantages of physical stimuli over traditional approaches. In particular, we will critically discuss recent results obtained by using optical stimulation, as a novel strategy to drive endothelial colony forming cells fate and its potential in the treatment of cardiovascular diseases.
Highlights
The vascular network is indispensable for all organisms to distribute oxygen (O2) and nutrients to the tissues and to remove carbon dioxide and other metabolic waste products (Heinke et al, 2012)
Therapeutic angiogenesis (TA) represents a promising strategy that aims at reconstructing the damaged vascular network by stimulating the regrowth of the endothelial cell layer that lines the inner lumen of blood vessels and plays a crucial role in adjusting blood supply according to local energy demand (Qadura et al, 2018; Prasad et al, 2020)
TRPV1-mediated uptake of anandamide stimulates Endothelial colony forming cells (ECFCs) migration (Hofmann et al, 2014), whereas TRPV4mediated nitric oxide release promotes the pro-angiogenic effects of arachidonic acid (AA) (Zuccolo et al, 2016)
Summary
The vascular network is indispensable for all organisms to distribute oxygen (O2) and nutrients to the tissues and to remove carbon dioxide and other metabolic waste products (Heinke et al, 2012). TRPV1-mediated uptake of anandamide stimulates ECFC migration (Hofmann et al, 2014), whereas TRPV4mediated nitric oxide release promotes the pro-angiogenic effects of AA (Zuccolo et al, 2016) It has, been suggested that targeting TRP channels could represent an efficient strategy to boost ECFCs’ regenerative potential (Moccia et al, 2015, 2018a). We depicted the molecular scenario observing that polymer photoexcitation led to a significant nuclear translocation of the Ca2+-sensitive transcription factor NF-kB and subsequent up-regulated the mRNA levels of specific pro-angiogenic genes (Figure 2B) Overall, these results start paving the way towards the use of conjugated polymers as reliable and efficient functional materials for precise and reversible optically-driven modulation of ECFC physiological activity
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