0000000000336580
AUTHOR
Giacomo Frati
showing 9 related works from this author
Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome
2019
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…
Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascen…
2018
AbstractBicuspid aortic valve (BAV) is frequently associated with the development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. For this purpose, 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; mean age: 69.1 ± 12.8 years) and AAA complicated or not, were included. Interestingly, patients with AAA showed a significant increase in circulating Notch1 levels and EPC number than subje…
Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases
2016
Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic stra…
Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers
2021
Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>
A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?
2018
Bicuspid valve disease is associated with the development of thoracic aortic aneurysm. The molecular mechanisms underlying this association still need to be clarified. Here, we evaluated the circulating levels of T and B lymphocyte subsets associated with the development of vascular diseases in patients with bicuspid aortic valve or tricuspid aortic valve with and without thoracic aortic aneurysm. We unveiled that the circulating levels of the MAIT, CD4+IL−17A+, and NKT T cell subsets were significantly reduced in bicuspid valve disease cases, when compared to tricuspid aortic valve cases in either the presence or the absence of thoracic aortic aneurysm. Among patients with tricuspid aortic…
An overview of the molecular mechanisms underlying development and progression of bicuspid aortic valve disease
2019
Bicuspid aortic valve (BAV) is a common congenital heart malformation frequently associated with the development of aortic valve diseases and severe aortopathy, such as aortic dilatation, aneurysm and dissection. To date, different genetic loci have been identified in syndromic and non- syndromic forms of BAV. Among these, genes involved in the regulation of extracellular matrix remodelling, epithelial to mesenchymal transition and nitric oxide metabolism appear to be the main contributors to BAV pathogenesis. However, no- single gene model explains BAV inheritance, suggesting that more factors are simultaneously involved. In this regard, characteristic epigenetic and immunological profiles…
Efficiency of transgenesis using sperm-mediated gene transfer: generation of hDAF transgenic pigs.
2000
SINCE the beginning of this century, replacement of failing human organs with their animal counterparts has been an interesting topic of debate for writers and scientists. In the 1960s, prolonged survival after kidney transplantation from chimpanzee to human was obtained in the United States and Europe. Nevertheless, both the progressive improvement in surgical technique and in immunosuppressant therapy and the availability of cadaveric organs and living donation have reduced the interest in xenotransplantation. Because of the increasing requests for organs and the lack of donors to meet that need, xenotransplantation has become a reliable option again for temporary organ replacement (eg, o…
Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function
2001
Up-regulation of proapoptotic genes has been reported in heart failure and myocardial infarction. To determine whether caspase genes can affect cardiac function, a transgenic mouse was generated. Cardiac tissue-specific overexpression of the proapoptotic gene Caspase3 was induced by using the rat promoter of α-myosin heavy chain, a model that may represent a unique tool for investigating new molecules and antiapoptotic therapeutic strategies. Cardiac-specific Caspase3 expression induced transient depression of cardiac function and abnormal nuclear and myofibrillar ultrastructural damage. When subjected to myocardial ischemia–reperfusion injury, Caspase3 transgenic mice showed increased inf…
Light on the molecular and cellular mechanisms of bicuspid aortic valve to unveil phenotypic heterogeneity
2019
Research on bicuspid aortic valve disease (BAV) and related complications has grown in an exponential manner in the last decades. However, the current knowledge of the mechanisms underlying the development of this disease is still limited, since all clinical and surgical studies on BAV mainly focused their objects on its major vascular complications, such as ascending aortic aneurysms and dissection. It is now clear that a better understanding of the pivotal molecular and cellular pathophysiological aspects of bicuspid valve aortopathy, including natural history, phenotypic expression, histology, cellular mechanisms and pathways, is critical for improving its clinical management. This chang…