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发布于:2020-11-27 11:17:42  访问:1 次 回复:0 篇
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Kaplan Neuroscience Pdf
Like IL and IL, plasma levels of IL correlate with increased cardiovascular risk.Preliminary data from CANTOS further indicate that plasma IL levels remain a determinant of residual risk, even after targeted IL inhibition.MCC also reduces infarct size and preserves ventricular function in pig models of myocardial infarction and has shown efficacy in the treatment of inflammatory disorders in man.Of recent interest, NLRP inhibition may have benefits in nonalcoholic steatohepatitis.In the future, orally available NLRP inhibitors will likely become available and require testing in various atherosclerotic settings.If targeting the NLRP inflammasome represents a step upstream in the IL signaling pathway, direct inhibition of IL represents a step downstream.As described above, in CANTOS, much of the benefit of IL inhibition was mediated through modulation of IL. Thus, direct targeting of IL with agents that either block IL binding merit consideration for atheroprotection.This observation is being corroborated in the ongoing ASSAIL. A recent phenomewide association study has further linked IL receptor variants with increased risks of aortic aneurysm, myocardial infarction, and chronic forms of atherosclerosis.In parallel to the CIRT trial of LDM, a trial of hydroxychloroquine to prevent recurrent events after myocardial infarction has been initiated.Hydroxychloroquine is an antimalarial with antiinflammatory properties used as secondline therapy in rheumatoid arthritis and lupus.It is reported that hydroxychloroquine may reduce TNF, IL, and IL production although the consistency and mechanisms of this effect are uncertain.Whether these buy Bleomycin Sulfate effects are independent of IL inhibition and can translate to human atherosclerosis requires further investigation.Further translational work is also needed for investigations of TREM, which has been shown to stimulate the inflammatory response after acute coronary ischemia.Supporting this concept, genetic variants in TREM may be associated with human coronary diseasean observation requiring largescale replication.Synthetic versions of these mediators are in development and have shown initial promise in ischemiareperfusion injury.Bioelectric therapy and stimulation of the autonomic inflammatory reflex represents a particularly novel mechanism to alter cytokine production.As expertly purchase Bleomycin Sulfate reviewed elsewhere, vaccination strategies designed to activate antiinflammatory components of the adaptive immune response have long shown promise.These effects are virtually identical in magnitude to those observed in CANTOS using an agent with powerful antiinflammatory properties in the absence of lipid lowering.There are several reasons to believe that therapy combining a PCSK inhibitor with an inhibitor of the IL to IL signaling pathway will provide at least additive effects.First, as shown a decade ago, there is virtually no relationship between ontreatment hsCRP and ontreatment LDLC, at least with statin therapy.The same observation has been made in CANTOS in reverse; absolute risk among those with low levels of hsCRP but elevated levels of LDLC remain substantially high.Combining aggressive LDL reduction with concomitant anticytokine therapy.The simple factorial design trial shown could be used to test both the independent and additive effects of lipid lowering and inflammation inhibition in the treatment of atherosclerosis.IL indicates interleukin; and PCSK, proprotein convertase subtilisinkexin type. In the simplest case, such combination therapy might include dual injections of both evolocumab and canakinumab.Alternatively, a bispecific monoclonal antibody could be constructed to simultaneously inhibit PCSK and IL.
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