心衰標(biāo)志物PDE-9A

1、講解人：郭君君The PDE super-family:a).contains 11 sub-genes conferring different cyclic nucleotide and tissue selectivity.b).PDE5A was the first cGMPselective enzyme discovered, and has a major role in erectile and pulmonary vasomotor control.c). PDE9A was cloned 20 years later and has the highest affinity

2、 and selectivity for cGMP .d).PDE9A is expressed primarily in the brain, gut and kidney.studies have focused on its role in cognitive function,and mRNA is detectable in the heart and other tissues.心臟肌肉健康是由兩種獨立機(jī)制心臟肌肉健康是由兩種獨立機(jī)制( (或信號通路或信號通路) )保保護(hù)護(hù) G G cGMPPKG心臟保護(hù)性心臟保護(hù)性“制動系統(tǒng)制動系統(tǒng)”NP激活激活PDE-9PDE-5 PF-961

3、3SILL-Arg +O2 NOS NO + 瓜氨酸瓜氨酸環(huán)化酶環(huán)化酶通路一L-NAMEDEANOODQ環(huán)化酶環(huán)化酶通路二DT3Figure 1 . PDE9A expression in heart and myocytes increases with disease.PDE9A upregulation by heart disease suggested its inhibition might blunt pathological stress responses.Figure 2. PDE9A inhibition suppresses cardiachypertrophy via

4、 natriuretic-peptidecGMP. Thus, opposite to PDE5A, PDE9A hydrolyses cGMP coupled to natriuretic peptide but not nitric oxide stimulation. Figure 3. Pressure-overload-induced cardiac pathobiology is suppressed in Pde9a-/-mice.結(jié)果，缺乏結(jié)果，缺乏PDE-9的小白鼠表現(xiàn)得更好。與正常的小白鼠心臟的小白鼠表現(xiàn)得更好。與正常的小白鼠心臟相比，缺乏相比，缺乏PDE-9的小白鼠心臟有更少的疤痕、肌肉變厚，擴(kuò)的小白鼠心臟有更少的疤痕、肌肉變厚，擴(kuò)張能力更強(qiáng)。張能力更強(qiáng)。PDE-5和PDE-9抑制劑對心功能的影響比較 i, RNCMs exposed to L-NAME and phenylephrine+/-Pde5a siRNA, Pde9a siRNA,or both. PE誘發(fā)小鼠心衰PDE-9抑制劑改善改善PDE-5抑制劑改善改善安慰劑完全心衰完全心衰結(jié)論結(jié)論:兩個通路相輔相成，保護(hù)一個通路就可避免疾兩個通路相輔相成，保護(hù)一個通路就可避免疾病發(fā)生，即使另一通路出現(xiàn)問題病發(fā)生，即使另一通路出現(xiàn)問題。前景精準(zhǔn)療法 PDE5抑制