The ratio Ratio between H eh CAMP and the fight against the proliferation of power prostacyclin analogues may not be obvious, but other strategies, hen to increased cAMP And amplified Strengths the effect of prostacyclin signaling may be useful, Especially when the prostano Administered by repeated inhalation. Phosphodiesterase enzymes, the r for the hydrolysis of cyclic nucleotides, and therefore Downstream essential role in the regulation of cAMP levels and Rts signaling in the kardiovaskul Re system. Eleven PDE families have been identified flt-3 inhibitors and these PDE4 is the main stock-specific PDE in lung and vascular System identified. PDE4 proteins Suspect are encoded by four genes that produce isolated many variants of PDE4 and rat studies, pulmonary arteries and PASMCs that these genes may be expressed fa Differential is in the Lungengef S. The presence of PDE4 in homogenates of large guest pulmonary artery of man has been studied, but not in the distal regions of the human Lungengef En.
In collaboration with PDE3 PDE4 enzyme family in the regulation of vascular Tonus pulmonary Acadesine involved relaxation causes PDE4 inhibitors and pulmonary artery preparations amplify agonist-induced vasodilator responses. On the other hand, the r PDE4 in Gef Structure modulation is unclear show studies that previously used alone can suppress PDE4 inhibitors migration of smooth muscle cells are isolated, but appear to be less effective to Vaskul Re inhibits smooth muscle cell proliferation. The mechanisms for the transformation of the pulmonary arteries in PAH multifactorial and include Abnormalit th Signal transduction by the TGF beta receptors and serotonin transporter, Kaliumkan Le, endothelium-derived factors and growth factors.
Proteolytic enzymes are also soup Ata included confinement, Lich elastase and metalloproteinases such as matrix gelatinases MMP 2 and MMP 9, which will break down collagen and elastin, regulate contribute a levy of extracellular Ren matrix, and the smooth muscle cell migration and proliferation. The activation of these enzymes leads to the production of ECM protein tenascin-C, which acts as a survival factor, proliferation and F Promotion of apoptosis in PASMCs deletion. R Which added a potentially important and MMP 2 is the regulation of vascular Tone and structure. By the cleavage of vasoactive peptides In patients with PAH, MMP 2 and MMP type 1 cell surface membrane Chemical activator of MMP 2 are located together in pulmonary Vaskul Re L Missions and isolated PASMCs exhibit gelatinase activity of t Compared with controls obtained Ht.
Previous studies involving the cAMP signaling pathway in the regulation of MMP 2 and MMP Production and have 9 Tten proposed in different human cell types. cAMP agents risers have also been found at the activity t of MMPs suppress and MT1 upregulate tissue inhibitors of MMPs, but it is not certain that agents such as inhibitors of prostacyclin and PDE gelatinase activity t modulate in human PASMCs. We have tried, the expression of genes D PDE4A human distal PASMCs contribution of PDE4 in cAMP hydrolytic activity of t In these cells, and to determine r With the PDE4 in regulating cAMP levels, the DNA synthesis, proliferation, apoptosis, and gelatinase activity t.