Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases.
Giorgia PierelliRosita StanzioneMaurizio ForteSerena MigliarinoMarika PerelliMassimo VolpeSperanza RubattuPublished in: Oxidative medicine and cellular longevity (2017)
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin) and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin) are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.
Keyphrases
- oxidative stress
- blood pressure
- type diabetes
- cardiovascular disease
- diabetic rats
- binding protein
- poor prognosis
- endothelial cells
- genome wide
- cell proliferation
- dna damage
- metabolic syndrome
- magnetic resonance imaging
- magnetic resonance
- copy number
- ischemia reperfusion injury
- insulin resistance
- nitric oxide synthase
- amino acid
- cell death
- induced apoptosis
- signaling pathway
- body mass index
- adipose tissue
- weight gain
- dna methylation
- physical activity
- genome wide identification
- glycemic control
- induced pluripotent stem cells
- reactive oxygen species
- transcription factor