Table 3.
FPR2 involvement in cardiovascular diseases (CVDs).
| CVDs | Expression and/or Stimulation | Effects |
|---|---|---|
| Atherosclerotic lesions | FPR2 stimulation with SAA hc and mc |
Detrimental effects contributing to atherosclerosis progression in human aortic endothelial cells (HAECs) [116] |
| Detrimental effects contributing to atherosclerosis progression upregulating the secretion of long pentraxin 3 (PTX3) in human aortic endothelial cells [116] | ||
| Detrimental effects by upregulating oxidized low-density lipoprotein (oxLDL) contributing to macrophages differentiation into foam cells and in turn inflammatory cytokine production and plaque formation [114] | ||
| FPR2 mRNA levels h and m (up-regulated expression) | Dual role by promoting both disease progression (detrimental) and plaque stability (beneficial) [101] | |
| FPR2 stimulation with AnxA1 m | Protective role by reducing sizes and macrophage accumulation in the atherosclerotic lesion [103] | |
| Protective effects by reducing the progression of existing plaques of aortic arch and subclavian artery by FPR2 dependent reduction of neutrophil rolling and adhesion to activated endothelial cells [104] | ||
| Protective effects exerted by proresolving ANXA1 mimicking peptide Ac2-26 reduces experimental atherosclerosis in presence of a functional FPR2 [106] | ||
| FPR2 stimulation with lipoxinA4 m | Protective effects by reducing macrophage infiltration and apoptotic cells in atherosclerotic lesions [102] | |
| FPR2 stimulation with LL-37 m | Detrimental effects by contributing to plaque formation by priming circulating platelet and inducing thromboinflammation [118,119] | |
| Neovascularization | FPR2 stimulation with WKYMVm hc, m and rb | Beneficial effects by recruiting endothelial progenitor cells, contributing to neovascularization and promoting re-endothelialization [108,109] |
| Protective effects by inhibiting restenosis [110] | ||
| Ischemia reperfusion injury (IRI) | FPR2 stimulation with LXA4 or AnxaA1 m | Protective effects by counter regulating the inflammatory response during IRI [123,124] |
| FPR2 antagonist Boc2 m | Detrimental effects exerted by pre-ischemia Boc2 administration resulting in LXA4 abrogated production and impaired vascular reactivity [124] | |
| FPR2 stimulation with Ac2-26 r | Protective effects by preserving cardiomyocyte contractility related to the activation of PKC, p38, and KATP channels [70] | |
| FPR2 stimulation with SAA hc | Detrimental effects, contributing to atherosclerosis progression by upregulating the secretion of long pentraxin 3 (PTX3) in human aortic endothelial cells [116] | |
| FPR2 stimulation with RvD1 r | Protective effects by inhibiting inflammatory cascades; reducing IL-6, TNF-α and MPO levels; diminishing apoptosis by Akt phosphorylation, and attenuating IR-induced damage [126] | |
| Protective effects by reducing percent of infarction area, ameliorating short- and long-term neurological deficits trough the activation of Rac1/NOX2 signaling pathway [128] | ||
| FPR2 stimulation with CGEN-855A r and m | Cardioprotective effects in rat and murine myocardial IRI [130] | |
| FPR2 stimulation with 15-epi-16-(p-fluorophenoxy)-LXA4-methyl ester m | Protective effects in renal IRI models, by modulating cytokine and chemokine expression and neutrophil recruitment [131] | |
| FPR2 stimulation with compound 17b m and mc | Protective effects by reducing inflammatory responses associated with reperfusion after an acute MI [69] | |
| FPR2 stimulation with ZK-994 and ZK-142 m | Protective effects by inhibition of neutrophil accumulation in murine hind-limb IRI-induced second-organ lung injury [132] | |
| Abdominal aortic aneurysm (AAA) | FPR2 stimulation with LXA4 m | Protective role by limiting neutrophil inflammation [135,136] |
| Myocardial infarction (MI) | FPR2 stimulation with WKYMVm m | Cardiac protection by mobilizing circulating angiogenic cells, contributing to their homing to ischemic heart [62] |
| FPR2 stimulation with 15-epimer-LXA4 m | Protective effects by triggering early activation of the resolving phase and improving left ventricular function post-MI [138] | |
| FPR2 inactivation by WRW4 m | Detrimental effects leading leukocytes to nonresolving inflammation in acute MI [139] | |
| Fpr2 gene deletion m | Detrimental effects by impairing biosynthesis of specialized proresolving mediators amplifying unresolved inflammation after cardiac injury [140] |
Table legend: m = mouse; r = rat; h = human; hc = human cell; mc = murine cell; rb = rabbit.