Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1082-1087

Study of serum endoglin level in smoker and nonsmoker patients with erectile dysfunction


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 Submission10-Mar-2022
Date of Decision24-May-2022
Date of Acceptance29-May-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Yasmin A R. El Sayed
Bagour, Menoufia
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_80_22

Rights and Permissions
  Abstract 


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 Top


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 Top


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 Top


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.
Table 1: Clinical and sociodemographic data of the studied group

Click here to view


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.
Table 2: Laboratory investigations among the studied groups

Click here to view


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).
Table 3: Mean serum endoglin (ng/ml) level among the studied groups

Click here to view


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

Click here to view


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)

Click here to view



  Discussion Top


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 Top


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.



 
  References Top

1.
Dougherty P. Erectile dysfunction. Phy Assist Clin 2018; 3:113–127.  Back to cited text no. 1
    
2.
Roychoudhury S, Chakraborty S, Choudhury AP, Das A, Jha NK, Slama P, et al. Environmental factors-induced oxidative stress: Hormonal and molecular pathway disruptions in hypogonadism and erectile dysfunction. Antioxidants 2021; 10:837.  Back to cited text no. 2
    
3.
Al-Dujaili MN, Al-Khafaji KH, Al-Dujaili AN. Endoglin level in pulmonary arterial hypertension patients and its association with some criteria. J Pharma Sci Res 2018; 1:0975–1459.  Back to cited text no. 3
    
4.
Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ. Nitric oxide and atherosclerosis: an update. Nitric Oxide 2006; 15:265–279.  Back to cited text no. 4
    
5.
Rathouska J, Jezkova K, Nemeckova I, Nachtigal P. Soluble endoglin, hypercholesterolemia and endothelial dysfunction. Atherosclerosis 2015; 243:383–388.  Back to cited text no. 5
    
6.
Wiesmann F, Petersen SE, Leeson PM, Francis JM, Robson MD, Wang Q, et al. Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution magnetic resonance imaging. J Am Coll Cardiol 2004; 44:2056–2064.  Back to cited text no. 6
    
7.
Gonen B, Rubenstien AH. Determination of glycohemoglobin. Diabetologia 1978; 15:5–8.  Back to cited text no. 7
    
8.
Fossati P, Prenciphe L. Determination of serum triglyceride. Clin Chem 1982; 28:207–210.  Back to cited text no. 8
    
9.
Van Hemelrijck M, Kessler A, Sollie S, Challacombe B, Briggs K. The global prevalence of erectile dysfunction: a review. BJU Int 2019; 124:587–599.  Back to cited text no. 9
    
10.
Blázquez-Medela AM, García-Ortiz L, Gómez-Marcos MA, Recio-Rodríguez JI, Sánchez-Rodríguez A, López-Novoa JM, et al. Increased plasma soluble endoglin levels as an indicator of cardiovascular alterations in hypertensive and diabetic patients. BMC Med 2010; 8:1–2.  Back to cited text no. 10
    
11.
Terentes-Printzios D, Ioakeimidis N, Rokkas K, Vlachopoulos C. Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs. Nat Rev Cardiol 2022; 19:59–74.  Back to cited text no. 11
    
12.
Caliri AW, Tommasi S, Besaratinia A. Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat Res 2021; 787:108365.  Back to cited text no. 12
    
13.
Ni H, Xu S, Chen H, Dai Q. Nicotine modulates CTSS (cathepsin S) synthesis and secretion through regulating the autophagy-lysosomal machinery in atherosclerosis. Arterioscler Thromb Vasc Biol 2020; 40:2054–2069.  Back to cited text no. 13
    
14.
Chen Y, Zhou B, Yu Z, Yuan P, Sun T, Gong J, et al. Baicalein alleviates erectile dysfunction associated with streptozotocin-induced type I diabetes by ameliorating endothelial nitric oxide synthase dysfunction, inhibiting oxidative stress and fibrosis. J Sex Med 2020; 17:1434–1447.  Back to cited text no. 14
    
15.
Irwin GM. Erectile dysfunction. Prim Care 2019; 46:249–255.  Back to cited text no. 15
    
16.
Trebatický B, Žitňanová I, Dvořáková M, Országhová Z, Paduchová Z, Ďuračková Z, et al. Role of oxidative stress, adiponectin and endoglin in the pathophysiology of erectile dysfunction in diabetic and non-diabetic men. Physiol Res 2019; 68:623–631.  Back to cited text no. 16
    
17.
Xie W, You J, Zhi C, Li L. The toxicity of ambient fine particulate matter (PM2. 5) to vascular endothelial cells. J Appl Toxicol 2021; 41:713–723.  Back to cited text no. 17
    
18.
Kim H, Lee SH, Jung J, Hong S, Lim HS. Pharmacokinetic drug interaction between amlodipine and tadalafil: an open-label, randomized, multiple-dose crossover study in healthy male volunteers. Drug Des Dev Ther 2022; 16:425.  Back to cited text no. 18
    
19.
Shiri R, Hakama M, Häkkinen J, Tammela TL, Auvinen A, Koskimäki J. Relationship between smoking and erectile dysfunction. Int J Impot Res 2005; 17:164–169.  Back to cited text no. 19
    
20.
Yue XF, Shen CX, Wang JW, Dai LY, Fang Q, Long L, et al. The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes modelvia mitochondrial protection. Asian J Androl 2021; 23:249.  Back to cited text no. 20
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed386    
    Printed32    
    Emailed0    
    PDF Downloaded44    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]