Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction

Silvis, Max J. M.; Demkes, Evelyne J.; Fiolet, Aernoud T L; Dekker, Mirthe; Bosch, Lena; Hout, Gerardus P.J. van; Timmers, Leo; Kleijn, Dominique P. V. de

doi:10.1007/s12265-020-10049-w

Cited by 72 publications

(53 citation statements)

References 82 publications

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“…Due to the intimate relationship between the two organ systems, the concept of the cardiorenal syndrome has been developed [ 1 ]. As inflammation is one of the major drivers for most heart diseases [ 2 , 3 , 4 ], it is interesting to note that most renal diseases are also associated with inflammation [ 5 , 6 , 7 ]. Moreover, in early stages of renal dysfunction, when the glomerular function is still intact, systemic and local inflammation leads to downregulation of molecules that have renal protective effects [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial

et al. 2020

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A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 μg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.

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Section: Introductionmentioning

confidence: 99%

Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial

et al. 2020

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“…Moderate regulation of the inflammatory response after MI is very important to prevent HF; however, an excessive inflammatory response will lead to the deterioration of myocardial remodeling and dysfunction after MI. Many studies have found that NLRP3 is activated after MI, resulting in an enhanced inflammatory response and cardiac dysfunction [ 26 ]. To determine whether the effect of LQF and perindopril on improving cardiac function is related to the inflammasome, we studied the expression of NLRP3 inflammasome in the heart.…”

Section: Resultsmentioning

confidence: 99%

LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice

Xiao-qing

Zhao

Feng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Excessive activation of the nod-like receptor family pyrin domain containing 3(NLRP3) inflammasome plays a significant role in the progression of cardiac injury. In China, it has been well recognized that Chinese herbal medicine is markedly effective in treating cardiovascular diseases (CVDs). LuQi Formula (LQF) has been used clinically for more than 10 years and confirmed to be effective in improving cardiac function and inhibiting apoptosis. However, the specific mechanisms underlying its efficacy are mostly unknown. This study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. Purpose. In this study, we investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. Methods. Forty male C57BL/6 mice were randomly divided into four groups: the sham group, the model group, the LQF group, and the perindopril group, with a sample size (n) of 10 mice in each group. Except the sham group, the other groups received left anterior descending (LAD) coronary artery ligation to induce MI and then treated with LQF, perindopril, or saline. Six weeks after MI, echocardiography was used to evaluate cardiac structure and function. Myocardial tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson’s trichrome to analyse myocardial fibrosis. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. The expressions of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR. The expression of reactive oxygen species in myocardial tissue was detected by using a DCFH-DA probe. Results. Echocardiographic analysis showed that compared with the model group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the LQF and perindopril group were increased ( P < 0.05 ), left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end-systole (LVIDs) were reduced ( P < 0.05 ), and H&E and Masson’s trichrome staining of cardiac tissues showed that LQF and perindopril could partially reverse ventricular remodeling and alleviate myocardial fibrosis ( P < 0.05 ). WGA fluorescence results showed that compared with the model group, myocardial hypertrophy was significantly reduced in the LQF and perindopril group. We also found that LQF and perindopril reduce the oxidative stress response in the heart of MI mice. The protein expression of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, and Bax was downregulated in the LHF and perindopril treatment group, and Bcl-2 expression was upregulated. Conclusion. LQF and perindopril significantly attenuated cardiac injury and apoptosis in the MI model. In addition, we found that LQF effectively inhibited the activation of the NLRP3/ASC/caspase-1/IL-1β cascade, decreased inflammatory infiltration, delayed ventricular remodeling, and downregulated caspase-3/Bax signaling, which can effectively reduce the apoptosis of cardiomyocytes. Perindopril showed the same mechanism.

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“…Some researchers concluded that NLRP3 protein might not play a role in the acute development of MI due to low cardiac expression (84), which may explain the failure of colchicine to take positive results in patients with ACS. However, more evidence has proven that NLRP3 inflammasomemediated inflammation does have an important role in ACSs (77,85). On the other hand, studies have also shown that colchicine does not necessarily activate NLRP3 (86).…”

Section: Anti-inflammatory Effects Of Colchicine In Atherosclerotic Heart Disease Need Further Evaluationmentioning

confidence: 99%

Anti-inflammatory Therapy for Coronary Atherosclerotic Heart Disease: Unanswered Questions Behind Existing Successes

Chen

2021

Front. Cardiovasc. Med.

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Coronary atherosclerotic heart disease is a serious threat to human health. The results of the Canakinumab Anti-Inflammatory Thrombosis Outcome Study published in 2017 put an end to the perennial debate about the anti-inflammatory treatment of coronary atherosclerotic heart disease. In addition to interleukin 1β monoclonal antibody, interleukin 6 receptor antagonists and colchicine have also shown exciting results in clinical trials within the last 3 years. However, behind these successes, questions remain that need to be addressed. In this review, we summarize the successes and existing doubts of interleukin 1β antibodies, interleukin 6 receptor antagonists, and colchicine in the anti-inflammatory treatment of coronary atherosclerotic heart disease.

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Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction

Cited by 72 publications

References 82 publications

Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial

Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial

LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice

Anti-inflammatory Therapy for Coronary Atherosclerotic Heart Disease: Unanswered Questions Behind Existing Successes

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