Objective: Ovine pregnancy is associated with elevated levels of nitric oxide. Nitric oxide stimulates cyclic guanosine monophosphate (cGMP), which results in vascular smooth muscle relaxation/vasodilation. Phosphodiesterase type 5 regulates cGMP in the urogenital track. The present study was designed to determine message expression of phosphodiesterase type 5 in the myometrium, uterine vessels, and placentome of the sheep and phosphodiesterase type 5 protein expression in the maternal and fetal placentome.
Study Design: Tissue was collected from 5 nonpregnant and 5 pregnant anesthetized animals (gestational day = 134 +/- 4) and frozen at -80 degrees C. Optimized reverse transcription-polymerase chain reaction was performed on all tissues, and immunohistochemistry was performed on the placentome only.
Results: Phosphodiesterase type 5 messenger ribonucleic acid levels were significantly higher in the myometrium and placentome, compared with the maternal blood vessels. Phosphodiesterase type 5 protein was immuno-localized to the vascular smooth muscle of the maternal vessels, stroma, and placental capsule only.
Conclusion: Although phosphodiesterase type 5 messenger ribonucleic acid was present in the fetal placenta, phosphodiesterase type 5 protein was expressed only in maternally derived placental tissue. This suggests that regulation of cGMP levels and vascular tone in the umbilical circulation differs from the uterine circulation.
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http://dx.doi.org/10.1016/j.ajog.2005.05.054 | DOI Listing |
The main treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) is radical surgery, pulmonary thromboendarterectomy (PEA). However, about 40% of patients with CTEPH are inoperable due to distal pulmonary vascular lesions or the severity of hemodynamic disorders. Almost 30% of patients with CTEPH experience persistent or recurrent pulmonary hypertension after surgery, that requires a drug treatment with PAH-specific drugs.
View Article and Find Full Text PDFBackground: PLCG2 is signal-transduction protein identified as a potential drug target for the treatment of Alzheimer's disease (AD). PLCG2 is regulated by stimulation of the TREM2 pathway in microglia, which results in phagocytosis of beta-amyloid. PLCG2 catalyzes the cleavage of PI(4,5)P2 into IP3 and diacylglycerol, resulting in increased cell motility, phagocytosis, and proliferation in microglia.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Alzheimers Dement
December 2024
National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Background: Cilostazol, a selective type-3 phosphodiesterase inhibitor, ameliorates β-amyloid accumulation by facilitating intramural periarterial drainage.
Method: Patients with mild cognitive impairment were registered in the COMCID study, an investigator-initiated, double-blinded, multi-center, phase-II clinical trial. The primary endpoint was the Mini-Mental State Examination score.
Background: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!