Pin1 as Molecular Switch in Vascular Endothelium: Notes on Its Putative Role in Age-Associated Vascular Diseases.
Francesca FagianiMarieva VlachouDaniele Di MarinoIlaria CanobbioAlice RomagnoliMarco RacchiStefano GovoniCristina LanniPublished in: Cells (2021)
By controlling the change of the backbones of several cellular substrates, the peptidyl-prolyl cis-trans isomerase Pin1 acts as key fine-tuner and amplifier of multiple signaling pathways, thereby inducing several biological consequences, both in physiological and pathological conditions. Data from the literature indicate a prominent role of Pin1 in the regulating of vascular homeostasis. In this review, we will critically dissect Pin1's role as conformational switch regulating the homeostasis of vascular endothelium, by specifically modulating nitric oxide (NO) bioavailability. In this regard, Pin1 has been reported to directly control NO production by interacting with bovine endothelial nitric oxide synthase (eNOS) at Ser 116 -Pro 117 (human equivalent is Ser 114 -Pro 115 ) in a phosphorylation-dependent manner, regulating its catalytic activity, as well as by regulating other intracellular players, such as VEGF and TGF-β, thereby impinging upon NO release. Furthermore, since Pin1 has been found to act as a critical driver of vascular cell proliferation, apoptosis, and inflammation, with implication in many vascular diseases (e.g., diabetes, atherosclerosis, hypertension, and cardiac hypertrophy), evidence indicating that Pin1 may serve a pivotal role in vascular endothelium will be discussed. Understanding the role of Pin1 in vascular homeostasis is crucial in terms of finding a new possible therapeutic player and target in vascular pathologies, including those affecting the elderly (such as small and large vessel diseases and vascular dementia) or those promoting the full expression of neurodegenerative dementing diseases.
Keyphrases
- nitric oxide
- nitric oxide synthase
- endothelial cells
- cell proliferation
- systematic review
- oxidative stress
- cardiovascular disease
- signaling pathway
- type diabetes
- poor prognosis
- cell death
- metabolic syndrome
- machine learning
- mild cognitive impairment
- epithelial mesenchymal transition
- adipose tissue
- skeletal muscle
- cell cycle
- insulin resistance
- transforming growth factor
- weight loss
- long non coding rna
- pi k akt
- big data
- cognitive impairment
- single molecule
- glycemic control
- protein kinase