Multiple Plasma Biomarkers for Risk Stratification in Patients With Heart Failure and Preserved Ejection Fraction

Chirinos, Julio A.; Orlenko, Alena; Zhao, Lei; Basso, Michael; Cvijic, Mary Ellen; Li, Zhuyin; Spires, Thomas E.; Yarde, Melissa; Wang, Zhaoqing; Seiffert, Dietmar; Prenner, Stuart B.; Zamani, Payman; Bhattacharya, Priyanka; Kumar, Anupam; Margulies, Kenneth B.; Car, Bruce D.; Gordon, David; Moore, Jason H.; Cappola, Thomas P.

doi:10.1016/j.jacc.2019.12.069

Cited by 130 publications

(120 citation statements)

References 22 publications

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“…Marked elevations of circulating pro-inflammatory cytokines are consistently noted in heart failure patients, in both HFrEF and HFpEF subpopulations [ 10 , 11 ]. Cytokine levels are further increased in patients exhibiting an acute decompensation [ 12 ] and seem to predict clinical outcome [ 13 ]. Patients with ischemic cardiomyopathy in the absence of myocardial infarction exhibit induction of chemokines in chronically ischemic myocardial segments, accompanied by recruitment of inflammatory leukocytes [ 14 ].…”

Section: Inflammatory Cytokines In the Pathogenesis Of Chronic Heart mentioning

confidence: 99%

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Hanna

Frangogiannis

2020

Cardiovasc Drugs Ther

207

170

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Heart failure exhibits remarkable pathophysiologic heterogeneity. A large body of evidence suggests that regardless of the underlying etiology, heart failure is associated with induction of cytokines and chemokines that may contribute to the pathogenesis of adverse remodeling, and systolic and diastolic dysfunction. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 have been extensively implicated in the pathogenesis of heart failure. Inflammatory cytokines modulate phenotype and function of all myocardial cells, suppressing contractile function in cardiomyocytes, inducing inflammatory activation in macrophages, stimulating microvascular inflammation and dysfunction, and promoting a matrixdegrading phenotype in fibroblasts. Moreover, cytokine-induced growth factor synthesis may exert chronic fibrogenic actions contributing to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In addition to their role in adverse cardiac remodeling, some inflammatory cytokines may also exert protective actions on cardiomyocytes under conditions of stress. Chemokines, such as CCL2, are also upregulated in failing hearts and may stimulate recruitment of pro-inflammatory leukocytes, promoting myocardial injury, fibrotic remodeling, and dysfunction. Although experimental evidence suggests that cytokine and chemokine targeting may hold therapeutic promise in heart failure, clinical translation remains challenging. This review manuscript summarizes our knowledge on the role of TNF-α, IL-1, IL-6, and CCL2 in the pathogenesis of heart failure, and discusses the promises and challenges of targeted anti-cytokine therapy. Dissection of protective and maladaptive cellular actions of cytokines in the failing heart, and identification of patient subsets with overactive or dysregulated myocardial inflammatory responses are required for design of successful therapeutic approaches.

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Section: Inflammatory Cytokines In the Pathogenesis Of Chronic Heart mentioning

confidence: 99%

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Hanna

Frangogiannis

2020

Cardiovasc Drugs Ther

207

170

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“…HFpEF is characterized as a contractile dysfunction with normal EF; it represents endothelial dysfunction, which is induced by comorbidities such as ageing, hypertension, diabetes, and obesity. In one recent study, an analysis of blood samples from HFpEF patients revealed that Ang2 was one of the predictive biomarkers for HF-related hospital admission [55]. This indicates that Ang2 levels may reflect endothelial damage and the severity of HFpEF.…”

Section: Ang-tie Pathway In Ischemic Heart Disease Stroke and Heartmentioning

confidence: 99%

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Hayashi

Rakugi

Morishita

2020

Cells

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Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected to permit clinical applications, especially in antiangiogenic therapies against tumors. Several drugs targeting the Ang-TIE signaling pathway in cancer patients are under clinical development. Similar to how cancer increases with age, unsuitable angiogenesis or endothelial dysfunction is often seen in other ageing-associated diseases (AADs) such as atherosclerosis, Alzheimer’s disease, type 2 diabetes, chronic kidney disease and cardiovascular diseases. Thus, the Ang-TIE pathway is a possible molecular target for AAD therapy. In this review, we focus on the potential role of the Ang-TIE signaling pathway in AADs, especially non-cancer-related AADs. We also suggest translational insights and future clinical applications of this pathway in those AADs.

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“…Indeed, in the past years, Wang et al [ 31 ], measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study (CRP, BNP, NT-proBNP, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, homocysteine, and urinary albumin-to-creatinine ratio), and found that for assessing risk in individuals, the use of the 10 contemporary biomarkers only moderately added to standard risk factors. More recently, Chirinos et al [ 32 ] measured 49 plasma biomarkers from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial participants ( n = 379) using a Multiplex assay to assess the relationship between biomarkers and the risk of all-cause death or HF-related hospital admission. In this case, the authors found that various novel circulating biomarkers in key pathophysiological domains are predictive of outcomes in HFpEF, and they concluded that a multimarker approach coupled with machine-learning represents a promising strategy for enhancing risk stratification in HFpEF.…”

Section: Discussionmentioning

confidence: 99%

Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure

Brioschi

Gianazza

Agostoni

et al. 2021

IJMS

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Heart failure (HF) is a complex disease due to the intricate interplay of several mechanisms, which therefore implies the need for a multimarker strategy to better personalize the care of patients with HF. In this study, we developed a targeted mass spectrometry approach based on multiple reaction monitoring (MRM) to measure multiple circulating protein biomarkers, involved in cardiovascular disease, to address their relevance in the human HF, intending to assess the feasibility of the workflow in the disease monitoring and risk stratification. In this study, we analyzed a total of 60 plasma proteins in 30 plasma samples from eight control subjects and 22 age- and gender- matched HF patients. We identified a panel of four plasma proteins, namely Neuropilin-2, Beta 2 microglobulin, alpha-1-antichymotrypsin, and complement component C9, that were more abundant in HF patients in relation to disease severity and pulmonary dysfunction. Moreover, we showed the ability of the combination of these candidate proteins to discriminate, with sufficient accuracy, HF patients from healthy subjects. In conclusion, we demonstrated the feasibility and potential of a proteomic workflow based on MRM mass spectrometry for the evaluation of multiple proteins in human plasma and the identification of a panel of biomarkers of HF severity.

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Multiple Plasma Biomarkers for Risk Stratification in Patients With Heart Failure and Preserved Ejection Fraction

Cited by 130 publications

References 22 publications

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure

Insight into the Role of Angiopoietins in Ageing-Associated Diseases

Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure

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