Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Jadapalli, Jeevan Kumar; Halade, Ganesh V.

doi:10.1096/fj.201800254r

Cited by 24 publications

(19 citation statements)

References 119 publications

(143 reference statements)

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“…Accordingly, inhibiting MMP-12 diminishes neutrophilic apoptosis, causing a similar progression with exaggerated inflammations in mice after infarction. This supports a strong association between neutrophilic apoptosis and the effective post-MI wound healing [ 78 ].…”

Section: Strategies For Therapeutic Interventions That Target Immune supporting

confidence: 78%

Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction

2018

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Myocardial infarction triggers infiltration of several types of immune cells that coordinate both innate and adaptive immune responses. These play a dual role in post-infarction cardiac remodeling by initiating and resolving inflammatory processes, which needs to occur in a timely and well-orchestrated way to ensure a reestablishment of normalized cardiac functions. Thus, therapeutic modulation of immune responses might have benefits for infarct patients. While such strategies have shown great potential in treating cancer, applications in the post-infarction context have been disappointing. One challenge has been the complexity and plasticity of immune cells and their functions in cardiac regulation and healing. The types appear in patterns that are temporally and spatially distinct, while influencing each other and the surrounding tissue. A comprehensive understanding of the immune cell repertoire and their regulatory functions following infarction is sorely needed. Processes of cardiac remodeling trigger additional genetic changes that may also play critical roles in the aftermath of cardiovascular disease. Some of these changes involve non-coding RNAs that play crucial roles in the regulation of immune cells and may, therefore, be of therapeutic interest. This review summarizes what is currently known about the functions of immune cells and non-coding RNAs during post-infarction wound healing. We address some of the challenges that remain and describe novel therapeutic approaches under development that are based on regulating immune responses through non-coding RNAs in the aftermath of the disease.

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Section: Strategies For Therapeutic Interventions That Target Immune supporting

confidence: 78%

Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction

2018

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“…Our results highlight the need to not only understand mechanisms that dampen but also mechanisms that turn off inflammation [27, 33, 35, 36]. …”

Section: Discussionmentioning

confidence: 94%

“…In conclusion, inflammation resolution was a critical component of MI remodeling that occurred under sex-dependent mechanisms. Our results highlight the need to not only understand mechanisms that dampen but also mechanisms that turn off inflammation [ 27 , 33 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 94%

LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling

et al. 2018

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Sex differences in heart failure development following myocardial infarction (MI) are not fully understood. We hypothesized that differential MI signaling could explain variations in outcomes. Analysis of the mouse heart attack research tool 1.0 (422 mice; young = 5.4 ± 0.1; old = 23.3 ± 0.1 months of age) was used to dissect MI signaling pathways, which was validated in a new cohort of mice (4.8 ± 0.2 months of age); and substantiated in humans. Plasma collected at visit 2 from the MI subset of the Jackson Heart Study (JHS; a community-based study consisting of middle aged and older adults of African ancestry) underwent glycoproteomics grouped by outcome: (1) heart failure hospitalization after visit 2 (n = 3 men/12 women) and (2) without hospitalization through 2012 (n = 24 men/21 women). Compared to young male mice, the infarct region of young females had fewer, but more efficient tissue clearing neutrophils with reduced pro-inflammatory gene expression. Apolipoprotein (Apo) F, which acts upstream of the liver X receptors/retinoid X receptor (LXR/RXR) pathway, was elevated in the day 7 infarcts of old mice compared to young controls and was increased in both men and women with heart failure. In vitro, Apo F stimulated CD36 and peroxisome proliferator-activated receptor (PPAR)γ activation in male neutrophils to turn off NF-κB activation and stimulate LXR/RXR signaling to initiate resolution. Female neutrophils were desensitized to Apo F and instead relied on thrombospondin-1 stimulation of CD36 to upregulate AMP-activated protein kinase, resulting in an overall better wound healing strategy. With age, female mice were desensitized to LXR/RXR signaling, resulting in enhanced interleukin-6 activation, a finding replicated in the JHS community cohort. This is the first report to uncover sex differences in post-MI neutrophil signaling that yielded better outcomes in young females and worse outcomes with age.Electronic supplementary materialThe online version of this article (10.1007/s00395-018-0699-5) contains supplementary material, which is available to authorized users.

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“…In contained inflammatory exudates, coordinated lipid mediator class switching occurs in the course of acute inflammation and resolution (Figure 2) [23,69,70]. AA-derived LXA4 is the first PUFA-derived mediator found to have anti-inflammatory and pro-resolving activities [71,72]. Platelet-leukocyte interaction leads to the formation of LXA4 and LXB4, which stimulates the lipid signaling class switch by blocking the further recruitment of polymorphonuclear cells from post-capillary venules [73].…”

Section: Specialized Pro-resolving Mediators (Spms)mentioning

confidence: 99%

“…Similarly, MCTRs act as tissue protective and regenerative agents, with anti-inflammatory and pro-resolving properties [25]. Thus, MaRs and MCTRs are regulated during acute self-limited infectious-inflammation and possess many attributes that contribute to host defense, tissue regeneration, organ protection, and pain modulation [25,34,39,49,72].…”

Section: Marsmentioning

confidence: 99%

The Role of Maresins in Inflammatory Pain: Function of Macrophages in Wound Regeneration

Hwang

Chung

Kim

2019

IJMS

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Although acute inflammatory responses are host-protective and generally self-limited, unresolved and delayed resolution of acute inflammation can lead to further tissue damage and chronic inflammation. The mechanism of pain induction under inflammatory conditions has been studied extensively; however, the mechanism of pain resolution is not fully understood. The resolution of inflammation is a biosynthetically active process, involving specialized pro-resolving mediators (SPMs). In particular, maresins (MaRs) are synthesized from docosahexaenoic acid (DHA) by macrophages and have anti-inflammatory and pro-resolving capacities as well as tissue regenerating and pain-relieving properties. A new class of macrophage-derived molecules—MaR conjugates in tissue regeneration (MCTRs)—has been reported to regulate phagocytosis and the repair and regeneration of damaged tissue. Macrophages not only participate in the biosynthesis of SPMs, but also play an important role in phagocytosis. They exhibit different phenotypes categorized as proinflammatory M1-like phenotypes and anti-inflammatory M2 phenotypes that mediate both harmful and protective functions, respectively. However, the signaling mechanisms underlying macrophage functions and phenotypic changes have not yet been fully established. Recent studies report that MaRs help resolve inflammatory pain by enhancing macrophage phagocytosis and shifting cytokine release to the anti-inflammatory M2 phenotypes. Consequently, this review elucidated the characteristics of MaRs and macrophages, focusing on the potent action of MaRs to enhance the M2 macrophage phenotype profiles that possess the ability to alleviate inflammatory pain.

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Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Cited by 24 publications

References 119 publications

Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction

Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction

LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling

The Role of Maresins in Inflammatory Pain: Function of Macrophages in Wound Regeneration

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