scholarly journals Clinically relevant high levels of human C-reactive protein induces endothelial dysfunction and hypertension by inhibiting the AMPK-eNOS axis

2020 ◽  
Vol 134 (13) ◽  
pp. 1805-1819
Author(s):  
Lele Cheng ◽  
Liang Wang ◽  
Manyun Guo ◽  
Jinlong He ◽  
Yangyang Deng ◽  
...  

Abstract Successful treatment of resistant hypertension accompanied by elevated human C-reactive protein (hCRP) remains a key challenge in reducing the burden of cardiovascular diseases. It is still unclear whether clinically relevant high-level hCRP is merely a marker or a key driver of hypertension. Here, we investigated the role and mechanism of clinically relevant high level of hCRP in hypertension. Elevated blood pressure was observed in all three hCRP overexpression models, including adeno-associated virus 9 (AAV9)-transfected mice, AAV9-transfected rats and hCRP transgenic (hCRPtg) rats. hCRPtg rats expressing clinically relevant high-level hCRP developed spontaneous hypertension, cardiac hypertrophy, myocardial fibrosis and impaired endothelium-dependent relaxation. Mechanistically, studies in endothelial nitric oxide (NO) synthase (eNOS) knockout mice transfected with AAV9-hCRP and phosphoproteomics analysis of hCRP-treated endothelial cells revealed that hCRP inhibited AMP-activated protein kinase (AMPK)-eNOS phosphorylation pathway. Further, activation of AMPK by metformin normalized endothelial-dependent vasodilation and decreased the blood pressure of hCRPtg rats. Our results show that clinically relevant high-level hCRP induces hypertension and endothelial dysfunction by inhibiting AMPK-eNOS signaling, and highlight hCRP is not only an inflammatory biomarker but also a driver of hypertension. Treatment with metformin or a synthetic AMPK activator may be a potential strategy for vaso-dysfunction and hypertension in patients with high hCRP levels.

2013 ◽  
Vol 3 (2) ◽  
pp. 10-15
Author(s):  
Munevera Bećarević ◽  
◽  
Duška Bećirović ◽  
Azijada Beganlić ◽  
Olivera Batić-Mujanović ◽  
...  

Introduction: Factors of cardiovascular risk (CVR) are often grouped in cases with diabetes mellitus (DM) with significant increasment of risk for CV disease . The aim of this research is to determine the frequency of CVR and and total CVR in cases with DM and to investigate connection of CRP of other factors of CVR in total cardiovascular risks. Material and methods: In 92 cases with DM weist values were taken as well as body mass index (BMI), blood pressure, sugar in blood, cholesterol, triglycerides, C reactive protein (CRP) and according to SCORE system the 10 year period of CVR were determined. Results: Out of 92 tested cases with age 55,22± 8,3 years, 63,05% were males and 36,95% were women, 81,5% were with values of sugar in blood >7mmol/l, 44,6% were with values of HbA1C>7% and 63,0% >6,5%. The value of cholesterol were >4,5mmol/l in 87%, triglycerides >1,7mmol/l in 78.3% of tested cases. 81,5% of tested cases were overweight and 49% with larger weight values. Average cardiovascular factor according to SCORE system was 3, 92± 3,7% with significant difference among sexes (M-4,86; W-2,32, p<o,05). According to height value CRP (>3mg/l) 52% of tested cases were with high cardiovascular risk. There is significant positive correlation between CRP and cholesterol level (p<0, 01), triglycerides, blood in sugar, HbA1c and upper values of blood pressure (p<0, 05). Significant correlation between CRP and total cardiovascular risk (p=0, 63) was not evident. Conclusion: Cases with diabetes mellitus have high level of non regulated cardiovascular risk factors. Even though there is significant correlation between CRP and and pressure values, sugar in blood, HbA1c, cholesterol, triglycerides, significant correlation between CRP and total cardiovascular risk in cases with diabetes mellitus is not evident.


VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Henrik Rudolf ◽  
Naemi Wall ◽  
Renate Klaassen-Mielke ◽  
Ulrich Thiem ◽  
Curt Diehm ◽  
...  

Abstract. Background: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. Patients and methods: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. Results: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. Conclusions: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.


2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Sylwia Biegańska-Hensoldt ◽  
Danuta Rosołowska-Huszcz

One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions.Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS) and increased production of nitric oxide (NO) and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules – sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.


2015 ◽  
Vol 10 (1) ◽  
pp. 36-40
Author(s):  
Shamima Jahan ◽  
Qaz Shamima Akhter

Background: Smoking may cause systemic inflammation, and high level of serum high sensitive Creactive protein may be found in smoker as an indicator of inflammation.Objective: To assess the serum high sensitive C - reactive protein level in male smokers of Bangladesh.Methods: The present cross sectional study was carried out in the Department of Physiology, Dhaka Medical College, Dhaka between July 2013 and June 2014. Hundred apparently healthy male regular cigarette smokers aged 20 to 40 years who smokes at least 5 sticks of cigarette per day for the last 5 years were included as study group. They were further divided in to 5-10 years, 11-15 years, 16-20 years and 1-10 cigarette sticks, 11- 20 cigarette sticks, more than 20 cigarette sticks/day depending on the duration of smoking and also according to consumption of number of sticks/day respectively. Age matched 100 apparently healthy male nonsmokers were included for control. To assess their inflammatory status, serum hs-CRP level was estimated by particles enhanced immunonephelometry using BN Systems in the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. In addition, BMI and blood pressure were measured by standard method to observe their association with smoking.Results: The mean serum hs-CRP level was significantly higher in male smokers than that of non smokers which was progressively increased with duration of smoking and number of cigarette sticks consumed per day. Again, mean BMI was significantly lower and diastolic blood pressure was significantly higher in male smokers than those of non smokers.Conclusion: The result of this study can be concluded that serum hs-CRP level progressively increases with duration of smoking and number of cigarette sticks consumed per day in male smokers.Bangladesh Soc Physiol. 2015, June; 10(1): 36-40


2020 ◽  
Vol 15 (3) ◽  
pp. 227-239 ◽  
Author(s):  
Hader I. Sakr ◽  
Akef A. Khowailed ◽  
Reham S. Al-Fakharany ◽  
Dina S. Abdel-Fattah ◽  
Ahmed A. Taha

Background: Pre-eclampsia poses a significant potential risk of hypertensive disorders during pregnancy, a leading cause of maternal deaths. Hyperuricemia is associated with adverse effects on endothelial function, normal cellular metabolism, and platelet aggregation and adhesion. This study was designed to compare serum urate levels in normotensive pregnant women to those with pregnancy-induced hypertension, and to evaluate its value as a potential predictive marker of hypertension severity during pregnancy. Methods: A prospective, observational, case-control study conducted on 100 pregnant women in their third trimester. Pregnant women were classified into two groups (n=50) according to arterial blood pressure measurements: group I had normal blood pressure, and group II had a blood pressure of ≥ 140/90, which was further subdivided according to hypertension severity into IIa (pregnancy- induced hypertension, IIb (mild pre-eclampsia), and IIc (severe pre-eclampsia). Blood samples were obtained on admission. Serum urate, high sensitive C-reactive protein, and interleukin-1β levels, and lipid profile were compared among the groups. Results: A significant increase in the mean values of serum urate, C-reactive protein, and interleukin- 1β levels was detected in gestational hypertensives. In addition, there was a positive correlation between serum urate levels and C-reactive protein and interleukin-1β, as well as between serum urate levels and hypertension severity. Conclusion: Hyperuricemia and increased C-reactive protein and interleukin-1β serum levels correlate with the severity of pregnancy-induced hypertension, and these biomarkers may play a role in the pathogenesis of pre-eclampsia. Serum urate measurement is sensitive, reliable markers that correlate well with the severity of hypertension in pregnant females with pre-eclampsia.


2010 ◽  
Vol 95 (9) ◽  
pp. 4460-4464 ◽  
Author(s):  
E. Jobs ◽  
U. Risérus ◽  
E. Ingelsson ◽  
J. Helmersson ◽  
E. Nerpin ◽  
...  

Objective: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants. Methods: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr. Results: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 sd increase, 0.13; 95% confidence interval 0.07–0.19; P &lt; 0.001) and higher serum IL-6 (regression coefficient for 1 sd increase, 0.08; 95% confidence interval 0.01–0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index &lt;25 kg/m2, n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr. Conclusions: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Lise Lund Håheim ◽  
Kjersti S. Rønningen ◽  
Morten Enersen ◽  
Ingar Olsen

The predictive role of high-sensitivity C-reactive protein (hs-CRP), number of tooth extractions, and oral infections for mortality in people with and without diabetes is unclear. This prospective cohort study is a 12 1/2-year follow-up of the Oslo II study, a health survey in 2000. In all, 12,764 men were invited. Health information was retrieved from 6434 elderly men through questionnaire information, serum measurements, and anthropometric and blood pressure measurements. Diabetes was reported by 425 men. Distinct differences were observed in baseline characteristics in individuals with and without diabetes. In the diabetes group, age and hs-CRP were statistically significant whereas in the nondiabetes group, age, hs-CRP, number of tooth extractions, tooth extractions for infections and oral infections combined, nonfasting glucose, systolic blood pressure, total cholesterol, regular alcohol drinking, daily smoking, and level of education were independent risk factors. The number of tooth extractions <5 was inversely related whereas more extractions increased the risk. Multivariate analyses showed that hs-CRP was a significant predictor in persons with diabetes and tooth extractions and oral infections combined; the number of teeth extracted and hs-CRP were for persons without diabetes. Infection and inflammation were associated with mortality in individuals both with and without diabetes.


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