The Predictive Value of Plasma Galectin-3 for Ards Severity and Clinical Outcome

Xu, Zhiheng; Xi, Li; Huang, Yongbo; Mao, Pu; Wu, Sulong; Yang, Baoxin; Yang, Yuanyuan; Chen, Kangxie; Liu, Xiaoqing; Li, Yimin

doi:10.1097/shk.0000000000000757

“…Galectin‐3 activates many profibrotic factors, promotes fibroblast proliferation and transformation, and mediates collagen production . Higher levels of galectine‐3 have been associated with a worse prognosis in patients with acute respiratory distress syndrome . In our study, canrenone did not increase galectin‐3 levels, suggesting that fibrosis did not increase, even if an echocardiographic examination was not performed to confirm this.…”

Section: Discussionsupporting

confidence: 43%

Efficacy and safety of two dosages of canrenone as add‐on therapy in hypertensive patients taking ace‐inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE‐IT trial

Derosa

¹

,

Maffioli

²

,

D'Avino

³

et al. 2016

Cardiovascular Therapeutics

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Summary Aim To evaluate the effects of canrenone as add‐on therapy in patients already treated with angiotensin‐converting enzyme inhibitors ( ACE ‐I) or angiotensin II receptor blockers ( ARB s) and hydrochlorothiazide at the maximum dosage (25 mg/d). Method In this randomized, open‐label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE ‐I or ARB s and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure ( BP ), pulse pressure ( PP ), heart rate ( HR ), fasting plasma glucose ( FPG ), homeostasis model assessment insulin ( HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate ( eGFR ), plasma urea, aldosterone, B‐type natriuretic peptide ( BNP ), and galectin‐3. Results Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (−20.26 vs −23.68 mm Hg for SBP , and −10.58 vs −12.38 mm Hg for DBP ), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mE q/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin‐3 were recorded. Conclusion Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010‐023606‐13; ClinicalTrials.gov NCT 02687178.

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“…Gal-3 inhibition has been shown to reduce the release of these cytokines from immune cells ( Chen et al, 2015 ; Ren et al, 2019 ; Yip et al, 2017 ). Additionally, high Gal-3 is directly associated with worse outcomes and lower survival in ARDS patients ( Xu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…First, the most concerning sequelae of CSS is evolution to acute respiratory distress syndrome (ARDS), a condition which often leads to respiratory failure despite proactive measures such as mechanical ventilation and intubation ( Vabret et al, 2020 ). Elevated serum levels of Gal-3 are significantly associated with worse outcomes and lower survival in patients suffering from ARDS ( Xu et al, 2017 ). Additionally, significantly elevated levels of Gal-3 have been shown in the serum of patients suffering from severe COVID-19 as compared to those with mild disease ( De Biasi et al, 2020 ).…”

Section: Gal-3 In Severe Infection: Promoting Immunologic Sequelae Ofmentioning

confidence: 99%

Immunopathology of galectin-3: an increasingly promising target in COVID-19

Caniglia

¹

,

Asuthkar

²

,

Tsung

³

et al. 2020

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The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the “Cytokine Storm Syndrome” (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.

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“…Gal-3 inhibition has been shown to reduce the release of these cytokines from immune cells (Chen et al, 2015;Ren et al, 2019;Yip et al, 2017). Additionally, high Gal-3 is directly associated with worse outcomes and lower survival in ARDS patients (Xu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Immunopathology of galectin-3: an increasingly promising target in COVID-19

Caniglia

¹

,

Asuthkar

²

,

Tsung

³

et al. 2020

View full text Add to dashboard Cite

The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the “Cytokine Storm Syndrome” (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.

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The Predictive Value of Plasma Galectin-3 for Ards Severity and Clinical Outcome

Abstract: Higher levels of galectin-3 were significantly associated with disease severity and worse outcomes in ARDS patients.

Cited by 26 publications

References 30 publications

Efficacy and safety of two dosages of canrenone as add‐on therapy in hypertensive patients taking ace‐inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE‐IT trial

Efficacy and safety of two dosages of canrenone as add‐on therapy in hypertensive patients taking ace‐inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE‐IT trial

Immunopathology of galectin-3: an increasingly promising target in COVID-19

Immunopathology of galectin-3: an increasingly promising target in COVID-19

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