Rationale: Intracoronary infusion of bone marrow mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) has led to limited improvement in left ventricular (LV) function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. Objective: To test the hypothesis that peripheral blood (PB) cytokines predict bone marrow (BM) endothelial progenitor cell (EPC) colony outgrowth and cardiac function after AMI. Methods and Results: BM and PB samples were collected from 87 participants 14-21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB IL-6 negatively correlated with endothelial colony forming cell (ECFC) colony maximum in the BM of AMI patients (estimate ± SE (ESE) -0.13±0.05, P=0.007). BM from healthy individuals showed a dose-dependent decrease in ECFC colony outgrowth in the presence of exogenous IL-1β or IL-6 (P <0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein (PDGF-BB) correlated positively with BM-derived CFU-EC colony maximum (ESE 0.01 ± 0.002, P<0.001), multipotent mesenchymal stromal cell (MSC) colony maximum (ESE 0.01±0.002, P=0.002) in BM, and MSC colony maximum in PB (ESE 0.02±0.005, P<0.001. Conclusions: Two weeks after AMI, increased PB PDGF-BB was associated with increased BM function, while increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI.Clinical Trial Registrations: clinicaltrials.gov Identifiers: NCT00684060.
Pharmacology, Toxicology and Pharmaceutical Science
1
4%
Other
4
15%
Unknown
7
27%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 March 2020.
All research outputs
#16,725,651
of 25,382,440 outputs
Outputs from Circulation Research
#6,380
of 7,667 outputs
Outputs of similar age
#197,236
of 325,190 outputs
Outputs of similar age from Circulation Research
#99
of 130 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,667 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.6. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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We're also able to compare this research output to 130 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.
