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ORIGINAL ARTICLE |
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Year : 2022 | Volume
: 35
| Issue : 3 | Page : 1082-1087 |
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Study of serum endoglin level in smoker and nonsmoker patients with erectile dysfunction
Mustafa A Hammam1, Yasmin A R. El Sayed1, Heba S Bazid1, Eman A Abd El Gyd2
1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Menoufia, Egypt 2 Department of Biochemistry, and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
Date of Submission | 10-Mar-2022 |
Date of Decision | 24-May-2022 |
Date of Acceptance | 29-May-2022 |
Date of Web Publication | 29-Oct-2022 |
Correspondence Address: Yasmin A R. El Sayed Bagour, Menoufia Egypt
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/mmj.mmj_80_22
Objective This study aimed to investigate the relation between endoglin as an endothelial marker in smoker and nonsmoker patients with erectile dysfunction (ED). Background ED is a benign disorder, but it can have a significant effect on the quality of life of the patients, partners, and families. Patients and methods A prospective randomized study was conducted on 90 men having ED and attending the Andrology Clinic in Menoufia University Hospital during the period from October 2020 to March 2021. Results Regarding clinical data (P < 0.05), 33.3% of nonsmokers with ED had diabetes, whereas 36.7% of smokers with ED had diabetes and hypertension and 83.3% of control group had no commodities (P = 0.001). All smokers with ED and nonsmokers with ED had metabolic syndrome. BMI and waist circumference were significantly higher in nonsmokers with ED group than nonsmokers with ED and control groups. There was a statistically significant difference between smokers with ED and nonsmokers with ED regarding mean serum endoglin level, as it was higher in smokers than nonsmokers (17.6 ± 0.97 vs. 14.0 ± 0.17) (P < 0.001). Moreover, serum endoglin was higher in smokers with ED and in nonsmokers with ED than in the control group (9.23 ± 0.69) (P < 0.001). Conclusions Endoglin can be considered as the endothelial dysfunction marker in male smokers with ED.
Keywords: endoglin, endothelial dysfunction, erectile dysfunction, nonsmokers, smokers
How to cite this article: Hammam MA, El Sayed YA, Bazid HS, Abd El Gyd EA. Study of serum endoglin level in smoker and nonsmoker patients with erectile dysfunction. Menoufia Med J 2022;35:1082-7 |
How to cite this URL: Hammam MA, El Sayed YA, Bazid HS, Abd El Gyd EA. Study of serum endoglin level in smoker and nonsmoker patients with erectile dysfunction. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1082-7. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1082/359527 |
Introduction | | |
Although erectile dysfunction (ED) is a benign condition, it can substantially influence the quality of life of patients, partners, and families. The inability to establish or sustain an adequate penile erection for satisfactory sexual performance is defined as ED[1]. A 3-month term of ED persistence has been proposed as a realistic clinical guideline. Erection is the consequence of a delicate balance of messages from the central and peripheral nerve systems influencing neurotransmitters, resulting in arterial and venous alterations and erection[2].
Smoking promotes oxidative stress through the disruption of the dynamic equilibrium between oxidation and antioxidation processes. Smoking (or specific compounds in cigarette smoke) increases superoxide production by endothelial and smooth muscle cells, reduces acetylcholine-induced artery relaxation, and increases mRNA expression of proinflammatory cytokines like interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha[3]. In addition to the free radical burden posed by cigarette smoke, depletion of the endothelial nitric oxide synthase enzyme eNOS BH4 is likely to contribute to endothelial dysfunction in chronic smokers. Furthermore, cigarette smoking promotes an increase in the generation of vasoconstrictor eicosanoids that are both dependent and independent on cyclooxygenase[4]. Endoglin is a 180-kDa homodimeric integral membrane glycoprotein that modulates endothelial function by acting as a receptor for the transforming growth factor-beta superfamily, which plays a role in atherosclerosis progression. S-endoglin, a soluble version of endoglin formed by cleavage of the endoglin molecule's complete extracellular domain, has also been considered as an endothelial dysfunction marker[5]. ED is typically associated with metabolic illnesses that are accompanied by low-grade chronic inflammation, which has been proposed as a possible mediator of endothelial dysfunction. As a result, the goal of this research was to see if there is a link between ED in smokers and nonsmokers and the endothelium dysfunction marker endoglin.
Patients and methods | | |
A case–control study was conducted on 60 men having ED and attending the Andrology Clinic in the University Hospital and 30 age-matched healthy nonsmoker volunteers as a control group. The studied participants were divided into three groups: group I consisted of 30 smoker men having ED, group II consisting of 30 nonsmoker men having ED, and group III consisted of 30 apparently healthy age-matched nonsmoker volunteers. Ethical consideration: The Ethical Committee of the Faculty of Medicine, University Hospital, approved the study (record number: 122020DERM). Written informed consent was obtained from each participant after simple and clear explanation of the research objectives. Inclusion criteria were as follows: men having dysfunction, both smokers and nonsmokers. Exclusion criteria were as follows: patients with a clear psychogenic ED, testosterone deficiency, acute inflammatory diseases, and renal or hepatic insufficiency. All patients and controls were subjected to the following: the medical history included the patient's name, age, and smoking index. The smoking index was calculated by dividing the number of packs smoked each day by the number of years a person has been a smoker. One pack-year is 20 cigarettes (1 pack) each day for a year, 40 cigarettes per day for half a year, and so forth. A pack per year is equal to packs of cigarettes smoked in a year, or 7305 cigarettes (number of pack-years), divided by (number of packs smoked each day) (number of years as a smoker). For instance, a 40-year-old smoker who smoked 15 cigarettes per day for 30 pack-years (15/20)×40 = 30. A pack-year is equal to 20 cigarettes smoked every day for a year. For the past 6 years, someone with a three-pack-year 42 history has smoked 10 cigarettes every day. A person who has smoked 40 cigarettes (two packs) per day for 20 years has smoked 40 cigarettes (two packs) per day. Sexual history and severity of ED were determined by the IIEF-5 questionnaire. The IIEF-5 questionnaire was completed by patients and participants. The IIEF-5 questionnaire has a maximum score of 25 points[6]. The following score is used for describing erectile function: normal function (21–25 points), mild ED (16–20 points), moderate ED (11–15 points), and severe ED (11–15 points) are the four categories of ED (<10 points). Full clinical examination, including general examination and local genital examination, were carried out to exclude mechanical causes of ED as Peyronie's disease and signs of hypoandrogenism. Biochemical parameters such as serum glucose, triacylglycerides, glycated hemoglobin (HbA1c), and serum endoglin (ng/ml) were measured. Biochemical analysis was done as follows: after a 12-h overnight fast, each patient gave 6 ml of venous blood through sterile vein puncture, which was divided into three tubes. Overall, 2 ml blood was collected into a single EDTA tube, which was used for colorimetric measurement of HbA1c as a percentage of total hemoglobin using Teco diagnostics' kits[6]. Using the Spinreact (Barcelona, Spain) kit from Spain[7], for enzymatic colorimetric blood glucose testing, 1 ml of blood was inserted in a sodium fluoride tube. Overall, 3 ml of blood was drawn into a plain tube and allowed to coagulate for 10 min at 37°C before being centrifuged for 10 min at 4000 rpm. The clear supernatant serum was collected and stored at −80°C until serum triglyceride (TG) and serum endoglin were determined. The enzymatic colorimetric assay was utilized for determining serum TG through the use of the Spinreact kit from Spain[8]. Enzyme-linked immunosorbent assay was used for measuring serum endoglin (Sun Red Biotechnology Company, Shanghai, China).
Statistical analysis
Data were acquired, tabulated, and analyzed through the use of the Statistical Package of Social Science (SPSS), version 20 on an IBM personal computer (SPSS Inc., Chicago, Illinois, USA), where the following numbers were used. Analytical statistics were used for determining whether there was a possible link between the studied factors and the targeted disease, whereas descriptive statistics were used to present quantitative data and qualitative data in the form of numbers and percentages, as well as mean, SD, and range. The following tests of significance were used: the χ2 test (number 2) was employed to investigate the relationship between two qualitative variables. The analysis of variance (F) test is a statistical test for comparing three or more groups with normally distributed quantitative variables. The Kruskal–Wallis test (nonparametric test) is a statistical test for comparing three or more groups with quantitative variables that are not normally distributed. Spearman's correlation (r) is a statistical test for determining the relationship between two quantitative variables.
A P value greater than 0.05 was deemed statistically insignificant. A statistically significant P value of 0.05 was used.
Results | | |
Clinical and sociodemographic data of the studied group
[Table 1] shows that the age of the smokers in the ED group ranged from 35 to 63 years, whereas the age of nonsmokers varied from 42 to 63 years. The age of the controls was in the range of 32 to 63 years, with no significant age difference between cases and controls (P > 0.05). There was a big disparity between the cases and the controls. Regarding their clinical data (P < 0.05), 33.3% of nonsmokers with ED had diabetes, whereas 36.7% of smokers with ED had diabetes and hypertension and 83.3% of control group had no comorbidities (P = 0.001). All smokers with ED and nonsmokers with ED had metabolic syndrome. BMI and waist circumference were significantly higher in nonsmokers with ED group than nonsmokers with ED and control groups. Blood pressure was significantly higher in smokers with ED group than nonsmokers with ED and controls.
Laboratory investigations among the studied groups
[Table 2] shows that there was a significant difference between cases and controls regarding the mean level of TG and HbA1c (P < 0.05). Serum TG was significantly higher in the smoker group and HbA1c was higher in the nonsmoker group.
Mean serum endoglin (ng/ml) level among the studied groups
[Table 3] shows that there was a statistically highly significant difference between smokers with ED and nonsmokers with ED regarding mean serum endoglin level, as it was higher in smokers than nonsmokers (17.6 ± 0.97 vs. 14.0 ± 0.17) (P < 0.001). Moreover, serum endoglin was higher in smokers with ED and in nonsmokers with ED than in the control group (9.23 ± 0.69) (P < 0.001).
Relationship between degree of erectile dysfunction and serum endoglin (ng/ml) level among the smokers with erectile dysfunction group
[Table 4] shows that there was a significant relationship between the degree of ED and serum endoglin (ng/ml) level among the smokers with ED group. Mean serum endoglin was significantly lower in patients with mild ED and higher in cases with severe ED (P = 0.001). | Table 4: Relation between degree of erectile dysfunction and serum endoglin (ng/ml) level among the smoker and nonsmoker with erectile dysfunction group
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Correlation between serum endoglin level and age, clinical, and laboratory investigations among the smokers with erectile dysfunction group
[Table 5] shows that the level of serum endoglin was found to have significant positive correlation with BMI, waist circumference, and systolic and diastolic blood pressures (P = 0.011). The levels of serum endoglin and HbA1c had a strong positive correlation (P = 0.001). There was no significant correlation between serum level endoglin level and age, duration of ED, BMI, and TG among the smokers with ED group (P = 0.908). | Table 5: Correlation between serum endoglin level and age and clinical and laboratory investigations among smokers with erectile dysfunction group (n=30)
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Discussion | | |
ED is the inability to generate or sustain an erection long enough to engage in sexual activity[9]. Through elevated inflammation and oxidative stress, endothelial dysfunction is linked to poor vascular nitric oxide production by a pathophysiological cascade, NO generation, and reduced vasodilation[10]. ED and cardiovascular disease are linked by hypertension, diabetes mellitus, hypercholesterolemia, and smoking. The severity of ED is linked to a patient's cardiovascular risk and is a precursor to widespread atherosclerosis. ED can potentially be used as a predictor of future cardiovascular events because it is a measure of early subclinical coronary artery damage[11]. Smoking is linked to several illnesses, including cancer and immune-mediated inflammatory disorders. Tobacco smoke comprises a complex mixture of chemicals, including reactive oxygen and nitrogen species, which can cause cellular and subcellular damage to lipids, proteins, and nucleic acids. Smoking-induced reactive oxygen species and the oxidative stress they create, according to a growing body of research, play a major role in inflammation and carcinogenesis[12]. Endoglin is a 180-kDa homodimeric integral membrane glycoprotein acting as a receptor for the transforming growth factor-beta superfamily, modulating endothelial function, which contributes to the progression of atherosclerosis. S-endoglin, a soluble version of endoglin generated by cleavage of the complete endoglin molecule's extracellular region, has also been proposed as a marker of endothelial dysfunction.
Patients with type 2 diabetes had higher levels of S-endoglin in their blood, which was linked to the severity of diabetic vascular abnormalities[10]. The aim of the current study was to investigate the serum level of endoglin, which is considered a member of oxidative stress and endothelial dysfunction in patients with ED and its relation to smoking. To achieve our aim, we included 90 participants and divided them into three groups: group I, smoking ED patients; group II, nonsmoking ED patients; and group III, nonsmoker healthy volunteers as a control group. For each participant, after a thorough examination, serum endoglin level was measured by enzyme-linked immunosorbent assay. There was a significant difference between the ED groups (both smokers and nonsmokers) and the control group regarding serum endoglin level; it was higher in ED groups than controls. This was in agreement with the study by Ni et al.[13], who found a positive association between circulating S-endoglin and ED. Furthermore, the current study showed that smokers with ED had significantly higher serum level of endoglin than nonsmokers with ED. Moreover, serum endoglin level was positively correlated to smoking in the smoker group. To the best of our knowledge, no previous studies discussed the relation of endoglin to smoking in patients with ED, but our results might be explained as smoking is a known risk factor of endothelial dysfunction[14]. In addition, several studies showed elevation of other endothelial markers, including cytochrome P450, lipoxygenases, and cyclooxygenases in smokers[15]. This study presented significant relation between the degree of ED and serum endoglin (ng/ml) level among the smokers with ED group. Mean serum endoglin was significantly lower in patients with mild ED and higher in cases with severe ED (P = 0.001). The article by Trebatický et al.[16] indicated a significant relationship between the degree of ED in smokers and endoglin, as smoking provokes atherosclerosis and subsequently increases serum endoglin as a marker of endothelial function. In the ED group of smokers, a strong positive association was observed between serum endoglin levels and smoking index. Smoking causes the endothelium to deteriorate faster. Smoke particles that make their way into the circulatory system will come into contact with blood and the vascular endothelial cells that line the vessels in a monolayer[17]. This disrupts their regular function, which could have serious consequences in terms of the onset and progression of atherosclerosis[18]. A highly significant positive correlation was observed between serum endoglin level and HbA1c among the smokers with ED and nonsmokers with ED. This was in line with the study done by Shiri et al.[19]. Endoglin levels were higher in patients with ED with diabetes than in nondiabetic patients, according to the study. They discovered a link between basal glycemia and endoglin in diabetic patients, but not in nondiabetic people. In addition, the paper by Fossati and Prenciphe[8] discovered a higher level of endoglin in adolescents with type 1 diabetes, and some authors concluded that endoglin levels may rise in tandem with endothelial function deterioration before subclinical structural vascular abnormalities became apparent[10]. There were substantial positive connections between BMI, waist circumference, and endoglin level in both smokers and nonsmokers with ED. This is in agreement with Yue et al.[20]. Cardiometabolic illnesses, such as atherosclerosis, type 2 diabetes, and liver disease, are all linked to endothelial dysfunction, arterial hypertension, hyperglycemia, obesity-related insulin resistance, and hypercholesterolemia, as per WHO. In the smokers with ED group, there was a substantial negative connection between serum endoglin levels and systolic blood pressure and diastolic blood pressure. This is in agreement with Blázquez-Medela et al.[10], who reported that long-term cigarette smokers have greater blood pressure than nonsmokers. This is in line with the findings of Yue et al.[20], who discovered that Sol-endoglin levels are higher in diabetic patients with high systolic blood pressure. In smokers and nonsmokers with ED, no significant association was observed between blood endoglin level and age, which is consistent with Trebatický et al.[16], who found no significant link between serum endoglin and age in diabetic patients with ED.
Conclusion | | |
Endoglin being a marker of endothelial dysfunction could be used as an indicator of vascular insufficiency in patients with ED (having any of the cardiovascular risk factors such as smoking, diabetes, or hypertension) reflecting the severity of ED.
Regarding the exclusion criteria, we recommend in the future studies all patients with metabolic syndrome should be excluded.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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