Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

Coppini, Raffaele; Santini, Lorenzo; Palandri, Chiara; Sartiani, Laura; Cerbai, Elisabetta; Raimondi, Laura

doi:10.3389/fphar.2019.01420

Cited by 14 publications

(12 citation statements)

References 183 publications

(224 reference statements)

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“…Taking into account its hepatoprotective effect, ferulic acid has been shown to decrease the elevated serum levels of the liver marker enzymes, AST and ALT, in rats subjected to ethanol-induced hepatotoxicity [3]. Additionally, azetidin-2-ones have shown good inhibitory activity on human chymase-a chymotrypsin-like serine protease which is thought to play an important role in chronic inflammation [54,55].…”

Section: Discussionmentioning

confidence: 99%

Biological Evaluation of Azetidine-2-One Derivatives of Ferulic Acid as Promising Anti-Inflammatory Agents

et al. 2020

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The purpose of this study was to evaluate the in vivo biological potential of new azetidine-2-one derivatives of ferulic acid (6a–f). First, the in vivo acute toxicity of azetidine-2-one derivatives of ferulic acid on Swiss white mice was investigated and, based on the obtained results, it can be stated that the studied derivatives belong to compounds with moderate toxicity. The in vivo anti-inflammatory potential of these derivatives was determined in a model of acute inflammation induced by carrageenan in rats and in a chronic inflammation model induced in rats using the granuloma test. In the acute inflammation model, all the studied compounds had a maximum anti-inflammatory effect 24 h after administration, which suggests that these compounds may be classified, from a pharmacokinetic point of view, in the category of long-acting compounds. The most active compound in the series was found to be compound 6b. In the case of the chronic inflammation model, it was observed that the studied compounds (6a–f) reduced the formation of granulation tissue compared to the control group, having an intense effect of inhibiting the proliferative component. The most important inhibitory effect of inhibiting the proliferative component was recorded for compound 6b. Additionally, the investigation of liver function was performed by determining the serum levels of liver enzymes aspartate transaminase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and bilirubin (total and direct). The results showed that, in the series of azetidin-2-one derivatives, the liver enzymes concentration values were close to those recorded for the reference anti-inflammatories (diclofenac sodium and indomethacin) and slightly higher compared to the values for the healthy control group. At the end of the experiment, the animals were euthanized and fragments of liver, lung, and kidney tissue were taken from all groups in the study. These were processed for histopathological examination, and we noticed no major changes in the groups treated with the azetidine 2-one derivatives of ferulic acid compared to the healthy groups.

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Section: Discussionmentioning

confidence: 99%

Biological Evaluation of Azetidine-2-One Derivatives of Ferulic Acid as Promising Anti-Inflammatory Agents

et al. 2020

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“…In addition to cytokines, chemokines, and CAMs, inflammatory mediators also include enzymes, which play a crucial role in tissue remodeling and inflammatory response. Activated leukocytes and mast cells express a variety of proteolytic enzymes, particularly serine proteases that ultimately modulate an inflammatory response [ 167 ].…”

Section: Cross-talk Between Nrf2 and Inflammationmentioning

confidence: 99%

An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation

Saha¹,

Buttari²,

et al. 2020

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Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer’s disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Interestingly, Nrf2 is proved to contribute to the regulation of the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target. Recent studies showed a connection between the Nrf2/antioxidant response element (ARE) system and the expression of inflammatory mediators, NF-κB pathway and macrophage metabolism. This suggests a new strategy for designing chemical agents as modulators of Nrf2 dependent pathways to target the immune response. Therefore, the present review will examine the relationship between Nrf2 signaling and the inflammation as well as possible approaches for the therapeutic modulation of this pathway.

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“…Important etiologies of AF include surgical procedures [ 1 ], hyperthyroidism [ 2 ], myocardial infarction [ 3 ], and cardiomyopathies [ 4 ]. Although the potential pathophysiologic mechanisms of AF remain controversial, there has been increasing evidence that inflammation is involved in the pathogenesis of AF [ 5 – 7 ]. Laboratory tests showed that inflammatory biomarkers (high-sensitivity C-reactive protein) increased in patients with AF [ 8 ] and anti-inflammatory medications may reduce the morbidity of AF [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation

Chen

Jiang

2021

Aging

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Background: Despite growing evidence indicating that patients with inflammatory bowel disease (IBD) have an increased risk of atrial fibrillation (AF), owing to the potential biases of confounding effects and reverse causation, the specific relationship between IBD and AF remains controversial. The aim of this study is to determine whether there is a causal effect of IBD on AF. Methods: A two-sample Mendelian randomization (MR) study was performed to evaluate the causal effect of IBD on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and traits of interest were obtained from independent consortia with European populations. The dataset of IBD was acquired from genome-wide association studies (GWAS), including more than 75,000 cases and controls. A GWAS with 60,620 AF cases and 970,216 controls was used to identify genetic variation underlying AF. The causal effect was estimated using the multiplicative random effects inverse-variance weighted method (IVW), followed by sensitivity analysis. Results: Using 81 SNPs, there was no evidence to suggest an association between genetically predicted IBD and risk of AF with multiplicative random-effects IVW MR analysis (odds ratio = 1.0000, 95% confidence interval: 0.9994 1.0005, p = 0.88). Conclusion: As opposed to current assumptions, no substantial evidence was found to support a causal role of IBD in the development of AF.

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Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

Cited by 14 publications

References 183 publications

Biological Evaluation of Azetidine-2-One Derivatives of Ferulic Acid as Promising Anti-Inflammatory Agents

Biological Evaluation of Azetidine-2-One Derivatives of Ferulic Acid as Promising Anti-Inflammatory Agents

An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation

Mendelian randomization as an approach to assess causal effects of inflammatory bowel disease on atrial fibrillation

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