Monocyte Subsets and Inflammatory Cytokines in Acute Decompensated Heart Failure

Goonewardena, Sascha N.; Stein, Adam; Tsuchida, Ryan E.; Rattan, Rahul; Shah, Dhavan; Hummel, Scott L.

doi:10.1016/j.cardfail.2015.12.014

Cited by 31 publications

(31 citation statements)

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“…Our findings that both ANP and BNP are overexpressed in the pulmonary system along with IL-6 and Cathepsin L in rats with decompensated CHF, hint possible interaction between NPs and certain cytokines in the lungs. Support for this concept is derived from the observation that patients with acute decompensated heart failure (ADHF) exhibit higher levels of C-reactive protein (CRP) and IL-6 compared with healthy controls [ 40 ]. The interaction between NPs and cytokines was demonstrated by the administration of ANP to rats with acute kidney injury induced by I/R where it inhibited mRNA expression of TNF-α, IL-1β, and IL-6 in the lung and kidney.…”

Section: Discussionmentioning

confidence: 99%

Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation

et al. 2018

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Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention as evident by peripheral and lung edema. Although the pathogenesis of CHF remains largely unclarified, it is widely accepted that neurohormonal changes and inflammatory processes are profoundly involved in structural and functional deterioration of vital organs including, heart, kidney and lungs. Corin, a cardiac serine protease, is responsible for converting pro-ANP and pro-BNP to biologically active natriuretic peptides (NPs). Although the involvement of corin in cardiac hypertrophy and heart failure was extensively studied, the alterations in corin and PCSK6, a key enzyme in the conversion of procorin to corin, have not been studied in the pulmonary tissue. Thus, this study aims at examining the status of PCSK6/Corin in the lung of rats with CHF induced by the creation of aorto-caval fistula (ACF) between the abdominal aorta and vena cava in SD rats. Rats with ACF were divided into 2 subgroups based on the pattern of their daily sodium excretion, compensated and decompensated CHF. Placement of ACF led to cardiac hypertrophy, pulmonary congestion, and renal dysfunction, which were more severe in the decompensated subgroup, despite remarkable elevation of circulatory ANP and BNP levels. Corin mRNA and immunoreactive peptide were detected in pulmonary tissue of all experimental groups. However, the expression and abundance of pulmonary corin significantly increased in the decompensated animals, but not in the compensated ones. Noteworthy, the expression of PCSK6 and ANP/BNP in the pulmonary tissue followed a similar pattern as corin. The upregulation of pulmonary Corin/PCSK6 and NPs were accompanied by local activation of cathepsin L and certain cytokines including IL-6. In light of the anti-inflammatory role of NPs, we postulate that the obtained upregulation of pulmonary PCSK6/Corin along NPs in rats with decompensated CHF may represent a counterbalance response to the inflammatory milieu characterizing CHF especially in severe cases.

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Section: Discussionmentioning

confidence: 99%

Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation

et al. 2018

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“…Few studies have examined whether LVAD impact inflammatory cytokine levels, with one revealing that LVADs may reduce circulating IL‐6 and TNF‐α levels 1 month after implantation (Clark et al ., 2001), but another showing that CRP and IL‐8 (a neutrophil attracting chemokine) increase postimplantation (Grosman‐Rimon et al ., 2014). Interestingly, even medical management of acute decompensated HF can reduce innate immune activation (Goonewardena et al ., 2015). The relationship between alterations in cytokines post‐LVAD implantation or acute treatment of decompensated HF and frailty has not yet been investigated and should be the focus of future investigation.…”

Section: Leveraging Therapies For Hf—a Potential Opportunity To Informentioning

confidence: 99%

Pathophysiology of heart failure and frailty: a common inflammatory origin?

et al. 2017

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SummaryFrailty, a clinical syndrome that typically occurs in older adults, implies a reduced ability to tolerate biological stressors. Frailty accompanies many age‐related diseases but can also occur without overt evidence of end‐organ disease. The condition is associated with circulating inflammatory cytokines and sarcopenia, features that are shared with heart failure (HF). However, the biological underpinnings of frailty remain unclear and the interaction with HF is complex. Here, we describe the inflammatory pathophysiology that is associated with frailty and speculate that the inflammation that occurs with frailty shares common origins with HF. We discuss the limitations in investigating the pathophysiology of frailty due to few relevant experimental models. Leveraging current therapies for advanced HF and current known therapies to address frailty in humans may enable translational studies to better understand the inflammatory interactions between frailty and HF.

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“…14 Moreover, in acute HF, blood neutrophil count at hospital admissions was associated with long-term mortality, 15 whereas total blood monocytes were increased but with a shift of the monocyte subset profile towards that of healthy control after standard HF treatment. 16 Despite the growing evidence base linking HFpEF with chronic inflammation, the importance of blood leucocyte count as an immune activity index and its relationship to cardiovascular and mortality outcomes in HFpEF are poorly defined. We sought to evaluate the association between leucocyte count and clinical events in HFpEF patients and test the hypothesis that higher leucocyte count, reflective of heightened immune cell expansion, is associated with higher rates of adverse cardiovascular outcomes.…”

Section: Introductionmentioning

confidence: 99%

Leucocyte count predicts cardiovascular risk in heart failure with preserved ejection fraction: insights from TOPCAT Americas

et al. 2020

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Aims Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored. Methods and results The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P < 0.05). Conclusions Leucocyte count >7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.

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Monocyte Subsets and Inflammatory Cytokines in Acute Decompensated Heart Failure

Cited by 31 publications

References 31 publications

Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation

Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation

Pathophysiology of heart failure and frailty: a common inflammatory origin?

Leucocyte count predicts cardiovascular risk in heart failure with preserved ejection fraction: insights from TOPCAT Americas

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