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Review
. 2015 Jul;21(7):586-93.
doi: 10.1016/j.cardfail.2015.04.014. Epub 2015 May 14.

The Importance of NLRP3 Inflammasome in Heart Failure

Brittany Butts  1 , Rebecca A Gary  1 , Sandra B Dunbar  1 , Javed Butler  2
Affiliations
Review

The Importance of NLRP3 Inflammasome in Heart Failure

Brittany Butts et al. J Card Fail. 2015 Jul.

Abstract

Patients with heart failure continue to suffer adverse health consequences despite advances in therapies over the past 2 decades. Identification of novel therapeutic targets that may attenuate disease progression is therefore needed. The inflammasome may play a central role in modulating chronic inflammation and in turn affecting heart failure progression. The inflammasome is a complex of intracellular interaction proteins that trigger maturation of proinflammatory cytokines interleukin-1β and interleukin-18 to initiate the inflammatory response. This response is amplified through production of tumor necrosis factor α and activation of inducible nitric oxide synthase. The purpose of this review is to discuss recent evidence implicating this inflammatory pathway in the pathophysiology of heart failure.

Keywords: Heart failure; inflammasome; inflammation.

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Figures

Figure 1
Figure 1. The NLRP3 inflammasome
NLRP3 inflammasome is comprised of three proteins: NLRP3, ASC and pro-caspase-1. NRLP3 has three domains: leucine-rich repeats (LRR), NACHT domain, and a PYD domain. The adaptor protein ASC pairs with NLRP3 via PYD domains and with pro-caspase-1 via CARD domains. DAMP (danger-associated molecular patterns) activation via LRR triggers transcription of NLRP3 and pro-IL-1β. The fully assembled NRLP3 inflammasome activates caspase-1, leading to the activation and release of IL-1β and IL-18.
Figure 2
Figure 2
Proposed Pathway of Epigenetic Regulation of the Inflammasome in Heart Failure
See this image and copyright information in PMC

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