title: Hierarchical regulation of wound healing by NOD-like receptors in cardiovascular disease.
abstract: CONCLUSIONS
  Persistent nonmicrobial tissue injury leads to the nonlinear activation of integrated wound-healing pathways. In chronic cardiovascular diseases, local tissue undergoes dynamic remodeling involving both structural cells and professional innate immune cells in attempts to limit burden of injury. While the final effector mechanisms by which these different cellular populations participate in wound healing are functionally distinct, their upstream molecular signaling pathways can often be shared.
  
  
  BACKGROUND
  The NOD-like receptors (NLRs) are intracellular pattern recognition receptors that have been well characterized as key regulators of pro-inflammatory cytokine production in innate immune cells. However, recent evidence has shown that some NLR proteins are additionally expressed by resident structural cells despite negligible cytokine production. These results indicate the potential for noncanonical routes of innate immune signaling by NLRs within solid organ systems.
  
  
  RESULTS
  Here, we review the emerging functions of NLR proteins in professional immune and tissue-resident cells, and discuss the implications in wound healing during chronic cardiovascular diseases. Emphasis is placed on NLRP3 and its regulation of cardiac structure and function in response to injury. Specific cellular and subcellular signaling paradigms are also discussed.
  
  
  CONCLUSIONS
  The characterization of how NLRs participate in homeostasis during cellular injury is essential to develop their potential utility for therapeutic intervention in cardiovascular disease.
authors.affiliation: 1 Department of Medicine, Snyder Institute for Chronic Diseases , University of Calgary, Calgary, Canada .
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Bracey
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Duff
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Muruve
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D005355:Fibrosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011110:Polymorphism, Genetic; D015398:Signal Transduction / Q000276:immunology; D014945:Wound Healing
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human