0000000000154356
AUTHOR
Valeriana Cesarini
Type 5 phosphodiesterase (PDE5) and the vascular tree: from embryogenesis to aging and disease
Highlights • Vascular development depends on the timely differentiation of endothelial and smooth muscle cells, that mutually influence their developmental fate. • Endothelial and vascular smooth muscle cell (VSMC) compartments can mutually influence cell and tissue modifications during vascular aging and in vascular disease. • Keeping in mind that PDE5 is mainly expressed in VSMCs, we surveyed the literature on the role of PDE5 in vascular development, aging and disease. • Although most results have been obtained by PDE5 pharmacological inhibition, no data are available, to date, on vascular development, aging or disease following PDE5 genetic ablation.
Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome
AbstractBicuspid aortic valve (BAV) disease is recognized to be a syndrome with a complex and multifaceted pathophysiology. Its progression is modulated by diverse evolutionary conserved pathways, such as Notch-1 pathway. Emerging evidence is also highlighting the key role of TLR4 signaling pathway in the aortic valve pathologies and their related complications, such as sporadic ascending aorta aneurysms (AAA). Consistent with these observations, we aimed to evaluate the role of TLR4 pathway in both BAV disease and its common complication, such as AAA. To this aim, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mea…
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms
AbstractAneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMC…
Impact of age and gender on glioblastoma onset, progression, and management
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, while its frequency in pe-diatric patients is 10-15%. For this reason, age is considered one of the major risk factors for the development of GBM, as it correlates with cellular aging phenomena involving glial cells and favoring the process of tumor transformation. Gender differences have been also identified, as the incidence of GBM is higher in males than in females, coupled with a worse outcome. In this review, we analyze age-and gender-dependent differences in GBM onset, mutational landscape, clinical manifestations, and survival, according to the literature of the last 20 years, focusing on the major risk fa…