TABLE 1

Potential candidates for revascularization in brain CNS diseases where cerebral microvasculature is impaired

TargetNameFunctionCNS diseaseRef.
VEGFVascular endothelial growth factorCooperates with Angiopoietin-1 to mediate angiogenesis and vessel maturation in ischemic brain. Binds to Aβ peptides present in AD brain microvasculature, which might result in local deficiency of accessible VEGF, leading to cerebrovascular degeneration and reduced neuroprotection. Preliminary evidence suggests a relationship between vasculature, hypoxia and motor neuron survival in ALS.Focal cerebral ischemia, Alzheimer's disease, Amyotrophic lateral sclerosis and aging(Evans et al., 2013; Patel et al., 2010; Zhang et al., 2000; Zhang et al., 2002)
PlGFPlacental growth factorContributes to neuroprotection, angiogenesis, vessel growth and maturation, maintaining vessel permeability. Synergistic angiogenic role with VEGF-A in hypoxic conditions.Cerebral ischemia(Carmeliet et al., 2001; Freitas-Andrade et al., 2012)
ANGPTL4Angiopoietin-like 4Potent inducer of cerebral neovascularization under hypoxic conditions. May also serve as diagnostic biomarker in patients with clinically assessed vascular cognitive impairment.Alzheimer's disease, aging and ischemic stroke(Bersini et al., 2020; Bouleti et al., 2013; Chakraborty et al., 2018)
bFGFBasic fibroblast growth factorMaintains the integrity of cerebral microvasculature. Angiogenic and neuroprotective effects under hypoxia, promotes the proliferation and migration of pericytes via its interaction with PDGF-BB. Interacts with VEGF-A synergistically in promoting angiogenesis.Cerebral ischemia, ischemic stroke(Dordoe et al., 2021; Harrigan, 2003; Lyons et al., 1991; Nakamura et al., 2016)
αvβ3Integrin αvβ3Expressed in the activated microvessels of CNS endothelial cells in response to hypoxia. Essential function in the angiogenesis activation.Cerebral ischemia(Abumiya et al., 1999)
NAD+Nicotinamide adenine dinucleotideProtects the integrity of cerebral microvasculature by controlling endothelial cells cellular metabolism, energy production and survival.Aging(Csiszar et al., 2019)
MEOX2MEOX2 gene (also known as GAX)Promotes the angiogenic response of CNS endothelial cells to hypoxia, suppresses apoptosis and increases Aβ clearance efflux.Alzheimer's disease(Wu et al., 2005)
miR- 15a/16-1microRNA- 15a/16-1 clusterControls VEGF and FGF expression regulating angiogenesis and cerebral blood flow.Cerebral ischemia(Sun P et al., 2020; Yin et al., 2012)
miR-30amicroRNA-30aControls BBB damage, infarct volume and neurovascular deficit caused by zinc accumulation in microvessels under ischemia, targeting the ZnT4 zinc transporter.Ischemic stroke(Wang P et al., 2020)
miR-124microRNA-124Regulates cerebromicrovascular impairment, including the decline in microvascular density and reduced angiogenesis.Alzheimer's disease(Li et al., 2019a)
miR-126microRNA-126Regulates angiogenesis and neurogenesis by the proliferation and migration of endothelial cells.Focal cerebral ischemia(Qu et al., 2019)
miR-210microRNA-210Acute ischemic stroke patients with higher circulating blood miR-210 show better clinical outcomes. Circulating blood miR-210 level associates with brain miR-210 level in a mouse model of ischemia, representing a biomarker of brain injury and repair. Promotes vascular endothelial cell migration and tube formation under hypoxia, and associates with local increased levels of VEGF.Ischemic stroke(Zeng L et al., 2011; Zeng L et al., 2014)