Interleukin-1 Blockade in Cardiovascular Diseases: From Bench to Bedside

Buckley, Leo F.; Abbate, Antonio

doi:10.1007/s40259-018-0274-5

Cited by 29 publications

(15 citation statements)

References 58 publications

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“…and impaired left ventricular function (dP/dt max ) (9). Moreover, exposure to IL-1b impairs vascular endothelial function possibly via increased oxidative stress (36).…”

Section: Discussionmentioning

confidence: 99%

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy

Bakkar

Mougharbil

Mroueh

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1b. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible pro-inflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a non-hypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1b. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.

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“…and impaired left ventricular function (dP/dt max ) (9). Moreover, exposure to IL-1b impairs vascular endothelial function possibly via increased oxidative stress (36).…”

Section: Discussionmentioning

confidence: 99%

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy

Bakkar

Mougharbil

Mroueh

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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“…HF is characterized by systemic inflammation, as shown by elevated circulating levels of inflammatory biomarkers in patients that increase with progression of the disease (25). For one, systemic inflammation may be the result of HF by means of tissue hypoperfusion and neurohormonal activation (26), or inflammation may play a pathophysiologic role in HF (27, 28). It is suggested that the pro-inflammatory state contributes to the development and progression of HF, not only by impairing myocardial function but also by affecting other organs and tissues and thereby adding to other aspects of the HF syndrome including cachexia and anemia (25).…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction

Wezenbeek

Canada

Ravindra

et al. 2018

Front. Cardiovasc. Med.

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Background: Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.Methods: Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log10) and NT-proBNP (logN).Results: Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5–9.0] mg/L, and NT-proBNP levels were 377 [106–1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16 ± 4 mlO2•kg−1•min−1. CRP levels significantly correlated with peakVO2 in all patients (R = −0.350, p < 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, N = 109) (R = −0.282, p < 0.001) and in those with preserved EF (HFpEF, N = 57) (R = −0.459, p < 0.001). NT-proBNP levels also significantly correlated with peak VO2 in all patients (R = −0.330, p < 0.001) and separately in patients with HFrEF (R = −0.342, p < 0.001) and HFpEF (R = −0.275, p = 0.032). CRP and NT-proBNP did not correlate with each other (R = 0.05, p = 0.426), but independently predicted peak VO2 (R = 0.421, p < 0.001 and p < 0.001, respectively).Conclusions: Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.

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“…The results demonstrated that I/R stimuli could induce the expression of GSDMD in the rat heart, while β-Asarone treatment markedly decreased the cleavage and activation of this protein, which was consistent with the level of caspase-1 activity. And IL-1β, a key proinflammatory cytokine which was closely associated with myocardial infarction and myocardial I/R injury, 29,30) also acted as an indicator of pyroptosis for its releasing style--through the pyroptosis pores in membrane. 31) Present results showed that the functional expressions of GSDMD also paralleled with the serum level of IL-1β.…”

Section: Dissussionmentioning

confidence: 99%

Beta-Asarone Alleviates Myocardial Ischemia–Reperfusion Injury by Inhibiting Inflammatory Response and NLRP3 Inflammasome Mediated Pyroptosis

Xiao

Huang

Wang

et al. 2020

Biological & Pharmaceutical Bulletin

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Beta-asarone(β-Asarone), the major component of Acorus tatarinowii Rhizoma, has been proved to be muti-pharmacological activities including anti-inflammation, and which is effective in protecting the central nervous system. However, the effect of β-Asarone on myocardial ischemia-reperfusion injury (I/R) injury is not yet clear. This study used a rat model with 45minutes occlusion and 24hours releasing of proximal segment of left anterior descending coronary artery. The effects of β-Asarone on cardiac histopathology, myocardial infarction size, levels of cardiac troponin T(cTNT) , myeloperoxidase(MPO) and interleukin-1β(IL-1β), protein expressions of apoptosis-associated speck-like protein containing a CARD(ASC), Nod-like receptor protein 3(NLRP3), caspase-1and Gasdermin D(GSDMSD) , and left ventricular performance were studied respectively. Our results showed that administration of β-Asarone significantly improved the heart outcome after myocardial ischemia and reperfusion in terms of less infarction size and lower serum cTNT concentration. Further, β-Asarone treatment evidently inhibited inflammatory response with less granulocyte infiltration, mild tissue edema and lower tissue MPO content, it also suppressed NLRP3 signal pathway and cardiac cell's pyroptosis for less protein expressions of ASC and NLRP3, lower level cleavage activation of caspase-1and GSDMSD, and lower serum IL-1β concentration. Finally, β-Asarone treatment well preserved the left ventricular performance with higher ejection fraction and fractional shortening. The experimental results suggested that β-Asarone was protective against myocardial ischemia-reperfusion injury, in which inhibition of inflammatory response and suppression of NLRP3 inflammasome mediated pyroptosis were supposed to play a vital role.

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Interleukin-1 Blockade in Cardiovascular Diseases: From Bench to Bedside

Cited by 29 publications

References 58 publications

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction

Beta-Asarone Alleviates Myocardial Ischemia–Reperfusion Injury by Inhibiting Inflammatory Response and NLRP3 Inflammasome Mediated Pyroptosis

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