Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: A prospective observational study

Karampela, Ιrene; Christodoulatos, Gerasimos Socrates; Kandri, Evangelia; Antonakos, Georgios; Vogiatzakis, E.; Dimοpoulos, George; Armaganidis, Apostolos

doi:10.1016/j.cyto.2019.03.002

Cited by 38 publications

(42 citation statements)

References 40 publications

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“…Increased eNAMPT levels were additionally reported in non-metabolic chronic inflammatory diseases [i.e., osteoarthritis (103) and acute lung injury (ALI) (165,166)], characterized by systemic inflammation. eNAMPT also seems to play a role in several types of infections like sepsis (167,168) or intrauterine infection (chorioamnionitis) (169), and in autoimmune inflammatory diseases including psoriasis (170), rheumatoid arthritis (RA) (171) Crohn's disease (CD) and ulcerative colitis (UC) (172). Table 1 summarized main activities of i/eNAMPT in these pathological conditions.…”

Section: Nampt and Naprt As Biomarkers Of Chronic And Acute Inflammatmentioning

confidence: 99%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are two intracellular enzymes that catalyze the first step in the biosynthesis of NAD from nicotinamide and nicotinic acid, respectively. By fine tuning intracellular NAD levels, they are involved in the regulation/reprogramming of cellular metabolism and in the control of the activity of NAD-dependent enzymes, including sirtuins, PARPs, and NADases. However, during evolution they both acquired novel functions as extracellular endogenous mediators of inflammation. It is well-known that cellular stress and/or damage induce release in the extracellular milieu of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune functions through binding pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and activate inflammatory responses. Increasing evidence suggests that extracellular (e)NAMPT and eNAPRT are novel soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported in several metabolic and inflammatory disorders, including obesity, diabetes, and cancer, while eNAPRT is emerging as a biomarker of sepsis and septic shock. This review will discuss available data concerning the dual role of this unique family of enzymes.

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Section: Nampt and Naprt As Biomarkers Of Chronic And Acute Inflammatmentioning

confidence: 99%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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“…ACE2, angiotensin-converting enzyme 2; CHD, coronary heart disease; eNOS, endothelial nitric oxide synthase; GERD, gastro-esophageal reflux disease; HTN, hypertension; IFN, interferon; IL, Interleukin; IMV, invasive mechanical ventilation; MAFLD, metabolic associated fatty liver disease; MCP-1, monocyte chemoattractant protein-1; Mets, metabolic syndrome; NK, natural killer; NLRP3, NOD-like receptor family pyrin domain containing 3; NO, nitric oxide; PAI-1, plasminogen activator inhibitor-1; RAAS, renin-angiotensin-aldosterone system; T2DM, type 2 diabetes mellitus; TNF-α, tumor necrosis factor-α; Tregs, regulatory T cell. (All images are derived from the free medical site http://smart.servier.com/ by Servier licensed under a Creative Commons Attribution 3.0 Unported License) [127,128]. It would be of interest to assess the clinical utility of circulating adipokines as biomarkers of clinical severity and prognosis in patients with COVID-19 and obesity.…”

Section: Ob E S I T Y Pai-1 Thromboxanementioning

confidence: 99%

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

et al. 2021

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Purpose of Review A growing body of evidence suggests that obesity and increased visceral adiposity are strongly and independently linked to adverse outcomes and death due to COVID-19. This review summarizes current epidemiologic data, highlights pathogenetic mechanisms on the association between excess body weight and COVID-19, compares data from previous pandemics, discusses why COVID-19 challenges the “obesity paradox,” and presents implications in prevention and treatment as well as future perspectives. Recent Findings Data from meta-analyses based on recent observational studies have indicated that obesity increases the risks of infection from SARS-CoV-2, severe infection and hospitalization, admission to the ICU and need of invasive mechanical ventilation (IMV), and the risk of mortality, particularly in severe obesity. The risks of IMV and mortality associated with obesity are accentuated in younger individuals (age ≤ 50 years old). The meta-inflammation in obesity intersects with and exacerbates underlying pathogenetic mechanisms in COVID-19 through the following mechanisms and factors: (i) impaired innate and adaptive immune responses; (ii) chronic inflammation and oxidative stress; (iii) endothelial dysfunction, hypercoagulability, and aberrant activation of the complement; (iv) overactivation of the renin–angiotensin–aldosterone system; (v) overexpression of the angiotensin-converting enzyme 2 receptor in the adipose tissue; (vi) associated cardiometabolic comorbidities; (vii) vitamin D deficiency; (viii) gut dysbiosis; and (ix) mechanical and psychological issues. Summary Mechanistic and large epidemiologic studies using big data sources with omics data exploring genetic determinants of risk and disease severity as well as large randomized controlled trials (RCTs) are necessary to shed light on the pathways connecting chronic subclinical inflammation/meta-inflammation with adverse COVID-19 outcomes and establish the ideal preventive and therapeutic approaches for patients with obesity.

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“…In addition, the baseline resistin concentrations varied significantly between the included studies in the aforementioned meta-analysis (3.6-127.2 ng/ml). Similarly, there is evidence on the association between increasing resistin concentration and mortality in critically ill patients with sepsis [18] and traumatic brain injury [19], for instance.…”

Section: Plos Onementioning

confidence: 99%

Resistin is a risk factor for all-cause mortality in elderly Finnish population: A prospective study in the OPERA cohort

Parkkila¹,

Kiviniemi²,

Tulppo³

et al. 2021

PLoS ONE

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Objective Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people. Methods The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline. Results After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64–5.56, p<0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577–0.734), p<0.001 and an optimal cutoff value of 12.88 ng/ml. Conclusions Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors.

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Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: A prospective observational study

Cited by 38 publications

References 40 publications

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

Resistin is a risk factor for all-cause mortality in elderly Finnish population: A prospective study in the OPERA cohort

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