Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats.
Carla Letizia BuscetiMaria CotugnoFranca BianchiMaurizio ForteRosita StanzioneSimona MarchittiGiuseppe BattagliaFerdinando NicolettiFrancesco FornaiSperanza RubattuPublished in: International journal of molecular sciences (2020)
The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect of brain-specific UCP2 overexpression on blood pressure (BP), stroke occurrence and kidney damage in JD-fed SHRSP. Rats received a single i.c.v. injection of a lentiviral vector encoding UCP2 (LV-UCP2), or an empty vector. The brain delivery of LV-UCP2 significantly delayed the occurrence of stroke and kidney damage. The large reduction of proteinuria observed after LV-UCP2 injection was unexpected, because BP levels were unchanged. At the time of stroke, rats treated with LV-UCP2 still showed a large UCP2 upregulation in the striatum, associated with increases in OPA1 and FIS1 protein levels, and reductions in PGC1-α, SOD2, TNFα mRNA levels and NRF2 protein levels. This suggested UCP2 overexpression enhanced mitochondrial fusion and fission and reduced oxidative damage and inflammation in the striatum of JD-fed SHRSP rats. Our data suggest the existence of central mechanisms that may protect against hypertension-induced organ damage independently of BP, and strengthen the suitability of strategies aimed at enhancing UCP2 expression for the treatment of hypertensive damage.
Keyphrases
- oxidative stress
- atrial fibrillation
- blood pressure
- cell proliferation
- cerebral ischemia
- white matter
- risk assessment
- poor prognosis
- binding protein
- transcription factor
- resting state
- protein protein
- amino acid
- diabetic rats
- small molecule
- physical activity
- multiple sclerosis
- nitric oxide
- endothelial cells
- heart rate
- metabolic syndrome
- drug induced
- functional connectivity
- newly diagnosed
- combination therapy