Endothelial cells play a critical role in maintaining the integrity of vascular structure and function. Endothelial dysfunction is closely associated with the development and progression of cardiovascular diseases (CVDs) like hypertension (HTN) and atherosclerosis. Gut microorganisms significantly contribute to atherosclerosis and related CVDs. Helicobacter pylori (H. pylori) colonizes in human gastric epithelium in a significant portion of general population in the world. Patients with H. pylori infection have significantly increased risk for CVDs including atherosclerosis, HTN, coronary heart disease, and cerebrovascular disease especially in younger patients (< 65 years old). H. pylori infection significantly impairs vascular endothelial function through multiple mechanisms including increased reactive oxygen species production and oxidative stress, inflammation, decreased nitric oxide formation, modification of the expression of cytokines and microRNAs, abnormalities of lipid and glucose metabolisms, and exosomes-mediated pathways. Endothelial dysfunction associated with H. pylori infection is reversible in both animal model and human subjects. Accumulating data suggests that H. pylori infection is an important risk factor for endothelial dysfunction and CVDs especially in young patients. Screening young male population for H. pylori infection and treating accordingly could be an effective approach for early prevention of CVDs especially premature atherosclerosis associated with H. pylori infection.
- Helicobacter pylori
- endothelial dysfunction
- cardiovascular disease
Atherosclerosis is among the principal contributors to cardiovascular diseases (CVDs) especially coronary artery diseases (CAD) and stroke . Despite in-depth understanding of the traditional cardiovascular risk factors including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, smoking, and obesity, and effective control of these known risk factors, CVDs remain the leading cause of mortality and morbidity in developed countries including the US [2, 3]. It is worrisome that the decline of all cardiovascular mortality rate has been slowing down since 2011 . It is very problematic that patients presenting with ST elevation myocardial infarction over the past 20 years are getting younger , and the total number of death from CAD and stroke is projected to increase by about 18% by 2030 . Clearly, there are other risk factors that have not been defined, and yet contribute significantly to the development and progression of atherosclerosis and related CAD and stroke.
Gut microorganisms significantly contribute to the development of atherosclerosis and related CVDs [7, 8, 9]. The microaerophilic Gram-negative bacterium
Growing evidences indicate that
2. Brief overview on
H. pylori infection and cardiovascular diseases
The role of
A recent study, using a large database with a total of 208,196 patients diagnosed with peptic ulcer diseases, compared the cardiovascular outcome for subjects with and without
Helicobacter pylori infection and carotid atherosclerosis
The relationship between
Recently, a large patient database of 17,613 adult patients with carotid ultrasound examination and a 13C-urea breath
The data showed that, after adjusting for age, sex, body mass index, lipid profile, HTN, DM, and smoking,
H. pylori infection and endothelial dysfunction
H. pylori infection and endothelial dysfunction in patients
Endothelial cells play a critical role in maintaining the integrity of vascular structure and function. Endothelial dysfunction is an important contributing factor to the pathogenesis of CVDs including HTN and atherosclerosis . Early studies with small patient samples suggested that there was no clear association between chronic infections, including infection with Chlamydia pneumoniae, cytomegalovirus, Epstein–Barr virus, and
However, accumulating data clearly supports the concept that
One of the important questions is whether endothelial dysfunction associated with
In a recent study, the investigators carefully selected 18 young patients (both male and female) with
H. pylori infection and endothelial dysfunction in animal models
In the same recent study, the investigators used specific-pathogen-free male C57BL/6 mice to establish a mouse
Thoracic aorta was collected to evaluate endothelium-dependent relaxation to acetylcholine (Ach) and endothelium-independent relaxation to nitroglycerin (NTG) at week 1, 8, 12, and 24 after
Efforts were made to examine if eradication of
4.3 Potential mechanisms for the effect of
H. pylori infection on endothelial function
It is important to know how
5. Role of exosomes in mediating the effect of
H. pylori infection on endothelial function
To determine how
Further studies , using the serum exosomes from patients with CagA+
Studies were also performed to determine if blocking exosomes release with GW4869
6. Effect of
H. pylori infection on other cardiovascular risk factors
It is not surprising that
7. Significance and clinical implications
It is very concerning that cardiovascular mortality has been increasing since 2010 especially for males for unknown reasons . It is also reported that the patients with ST elevation myocardial infarction over the past 20 years are getting younger . The reasons for this reverse trend in cardiovascular mortality and mobility have yet to be defined.
There are substantial sex differences in many CVDs including (but not limited to) myocardial infarctions, heart failure, hypertension, and cardiac hypertrophy . It is well known that premenopausal women are relatively protected from CVDs when compared to men. Typically, women are almost 10 years older than men when they have their first myocardial infarction . It was believed that the decreased cardiovascular morbidity and mortality in young females was due to possible cardio-protective effects of estrogen . However, several large clinical studies, including the HERS trials and the Women’s Health Initiative study [91, 92] showed that hormone replacement therapies (HRT) had no cardiovascular benefit in post-menopausal women. In contrast, there might have been an increased risk of CAD during the first year of HRT, and there was an increased risk of nonfatal ventricular arrhythmias among the women on HRT . Thus, the mechanism(s) for decreased CVD risk in premenopausal women is still unclear. The prevalence of
Currently available data strongly suggest that
This work was supported by US NIH grant HL148196 (ZL).
Conflict of interest
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