Dataset Information

Leukocyte-Expressed ?2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury.

ABSTRACT: Immune cell-mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through ?-adrenergic receptors (?ARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown.Wild-type (WT) mice were irradiated followed by isoform-specific ?AR knockout (?ARKO) or WT bone-marrow transplantation (BMT) and after full reconstitution underwent MI surgery. Survival was monitored over time, and alterations in immune cell infiltration after MI were examined through immunohistochemistry. Alterations in splenic function were identified through the investigation of altered adhesion receptor expression.?2ARKO BMT mice displayed 100% mortality resulting from cardiac rupture within 12 days after MI compared with ?20% mortality in WT BMT mice. ?2ARKO BMT mice displayed severely reduced post-MI cardiac infiltration of leukocytes with reciprocally enhanced splenic retention of the same immune cell populations. Splenic retention of the leukocytes was associated with an increase in vascular cell adhesion molecule-1 expression, which itself was regulated via ?-arrestin-dependent ?2AR signaling. Furthermore, vascular cell adhesion molecule-1 expression in both mouse and human macrophages was sensitive to ?2AR activity, and spleens from human tissue donors treated with ?-blocker showed enhanced vascular cell adhesion molecule-1 expression. The impairments in splenic retention and cardiac infiltration of leukocytes after MI were restored to WT levels via lentiviral-mediated re-expression of ?2AR in ?2ARKO bone marrow before transplantation, which also resulted in post-MI survival rates comparable to those in WT BMT mice.Immune cell-expressed ?2AR plays an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration.

SUBMITTER: Grisanti LA

PROVIDER: S-EPMC5120587 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Leukocyte-Expressed β2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury.

Grisanti Laurel A LA Gumpert Anna M AM Traynham Christopher J CJ Gorsky Joshua E JE Repas Ashley A AA Gao Erhe E Carter Rhonda L RL Yu Daohai D Calvert John W JW García Andrés Pun AP Ibáñez Borja B Rabinowitz Joseph E JE Koch Walter J WJ Tilley Douglas G DG

Circulation 20160630 2

<h4>Background</h4>Immune cell-mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through β-adrenergic receptors (βARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown.<h4>Methods</h4>Wild-type (WT) mice were irradiated followed by isoform-specific βAR knockout (βARKO) or WT bone-marrow transplantation (BMT) and after f ...[more]

PMID: 27364164

Similar Datasets

Project description:BackgroundInflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction.MethodsIn this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes.ResultsWe enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002).ConclusionsIn this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.

Dataset Information

Leukocyte-Expressed ?2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury.

Publications

Leukocyte-Expressed β2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets