1、1Inflammation in heart failureLiao Yu-HuaInstitute of CardiologyUnion HospitalHuazhong University of Science and Technology, Wuhan China2Cognitive process of pathophysiology and therapy in haert failure FluidretentionHemodynamicabnormityNeurohormoneabnormityCytokines40-60 era 70-80 era 80-90 era 90
2、eraNeurohormoneantagonistExpand vessel/cardiotonic Diuretic ？3Inflammation and Heart failure1. Interaction between neuroendocrine and cytokines in heart failure 2. therapy between inflammation and heart failure4-adrenergic stimulation induces proinflammatory cytokine expression in myocardiummRNA exp
3、ression by Northern blotting protein levels by Western blotting*P0.01, *P0.0001 vs saline-treated animals.Murray et al. Circulation. 2000;101:2338-2341.In control myocardium, TNF-a,IL-1b and IL-6 were not detected. Isoproterenol infusion significantly increased expression of all 3 cytokines, indicat
4、ing that chronic -adrenergic stimulation was associated with proinflammatory cytokine expression.5Causal relationship between Ang II and TGF-1 in cardiac hypertrophySchultz JEJ, et al. J Clin Invest 2002;109:787 96The lack of the TGF1 gene fully prevented the development of cardiac hypertrophy induc
5、ed by subpressor doses of Ang II that was observed in wild type mice Ang II-induced cardiac hypertrophy is mediated by TGF-1 6Evidence for a connection between Ang II and TGF-1 in cardiac tissueStephan Rosenkranz.Cardiovascular Research 2004; 63:423 432Some studies indicate that Ang II and TGF-1 act
6、 in an auto-/paracrine manner, and suggest cross-talk between the various myocardial cell types and compartments 7Angiotensin II-induced myocardial TNF biosynthesis in the adult heart TNF mRNA expressionKalra D, et al. Circulation 2002; 105:2198 205.Treatment with Ang II resulted in a rapid increase
7、 in TNF mRNA synthesis in isolated buffer perfused hearts 8Angiotensin II induced activation of NF-BKalra D, et al. Circulation 2002; 105:2198 205.Stimulation with Ang II lead to a rapid increase in NF-B binding activity in isolated buffer perfused hearts, the finding suggest a possible pathway in A
8、ng II mediated TNF biosynthesis 9Cross-regulation between the renin-angiotensin system andinflammatory mediatorsK. Sekiguchi et al. Cardiovascular Research 2004； 63： 433442There is a complicated network in heart failure between neuroendocrine system and immune systemAng II provokes inflammatory resp
9、onses in the heart through an NF-B dependent pathway, whereas TNF provoke activation of the RAS in the heart through increased ACE activity. Both of these pathways converge on overlapping MAPK signal transduction pathways 10Inflammation and Heart failure1. Interaction between neuroendocrine and cytokines in heart failure2. therapy between inflammation and heart failure
