scholarly journals Male Subclinical Hypogonadism: Mechanisms with Interplay of Reproductive Hormones, Undercarboxylated Osteocalcin and Endothelial Dysfunction

Author(s):  
ragaa abdelshaheed matta ◽  
Hazem Mohamed Farrage ◽  
Ahmed Abdelfadel Saedii ◽  
Mohamed Mamdouh Abdelrahman

Abstract BackgroundPathogenesis and endothelial function in subclinical hypogonadism (SCH) are unknown. Undercarboxylated osteocalcin (ucOC) participate in atherosclerosis and reproduction. We studied interplay of endothelial function, unOC and reproductive hormones with SCH.Methodsamong SCH, late onset hypogonadism (LOH), and healthy eugonadal male (HC) groups, we measured sex hormones and unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product and estradiol/T (E/T) as indicators of impaired leydig cell, androgen sensitivity index (ASI) & aromatase activity respectively and regulators for LH set point. We assessed flow mediated dilation of brachial artery (FMD%), carotid- intima media thickness (CIMT) and aortic stiffness index (AS) as markers of subclinical atherosclerosis.ResultsContrary to LOH, SCH had higher ASI, lower E/T ratio& similar T, follicle stimulating hormone and sex hormone binding globulin (SHBG) compared to HC, LH/ T was significant higher in LOH and lower in HC than SCH . Similar to LOH, SCH had significant lower FMD% and higher CIMT, AS, unOC & inflammatory marker and atherogenic lipid profile than HC. LH, LH/T & ucOC negatively while T positively FMD% meanwhile. LH, LH/T & ucOC positively while testosterone negatively correlated with CIMT. LH and LH/T positively while estradiol and E/T negatively related to AS. ucOC positively correlated to LH, LH/T, E SHBG & negatively correlated with T. Independent predictors were LH for FMD% & AS meanwhile LH and LH/T for CIMT.ConclusionsSCH as not impaired testicular function state is characterized by androgen insensitivity, impaired aromatase activity, compensatory elevated unOC and atherogenic role of LH in endothelial dysfunction.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Davide Grassi ◽  
Richard Draijer ◽  
Giovambattista Desideri ◽  
Theo Mulder ◽  
Claudio Ferri

Introduction: Endothelial dysfunction is an early biomarker for the development of cardiovascular disease and a predictor of future cardiovascular events. A number of intervention studies in healthy and diseased subjects have reported that endothelial function, as assessed by flow-mediated vasodilation (FMD), is positively affected by black tea consumption. On the other hand, high calorie fatty meals are detrimental to endothelial function. Hypothesis: To assess the effect of black tea with and without a fat load on FMD, digital volume pulse (DVP) and office blood pressure (BP) in never treated grade 1 hypertensive subjects without additional cardiovascular risk factors. Methods: According to a randomized, double-blind, controlled, cross-over design, 19 grade 1 hypertensives were assigned to consume black tea, containing 150 mg polyphenols or a placebo drink matched for caffeine, color and taste, twice a day for eight days, with a wash-out period in between of 13 days. On day 7 all measurements were performed in a fasted state, while on day 8 subjects consumed ultra-heat-treated whipping cream (1 gram fat per kg bodyweight) 30 minutes after consuming the test products. FMD, DVP and BP were measured at baseline and 1, 2, 3 and 4 hours after consumption of the test products. Results: Baseline FMD improved after 1-week tea consumption when compared to placebo (p<0.0001). An additional cup of tea further increased FMD at 1, 2, 3 and 4 hours after consumption when compared to baseline with maximal response 2 hours after intake (p<0.0001). Fat challenge significantly decreased FMD (p<0.0001), which was counteracted by tea consumption. Tea improved reflection index (small vessel tone; p<0.0001) and stiffness index (large arterial stiffness; p<0.0001) with additional effects after acute tea consumption with and without fat load. Further, tea decreased systolic and diastolic BP with and without a fat load (all p<0.0001). Conclusions: We demonstrate for the first time that moderate consumption of black tea protects against oral fat load-induced endothelial dysfunction in hypertensive but otherwise healthy subjects. The vascular benefits of tea are also reflected in improved endothelial function and peripheral arterial hemodynamics as well as blood pressure lowering under fasted and postprandial conditions. Our findings are of clinical relevance and interest, considering that the ingestion of the main daily meal has been suggested to be a trigger for acute myocardial infarction.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tetsuzo Wakatsuki ◽  
Koji Yamaguchi ◽  
Toshiyuki Niki ◽  
Kenya Kusunose ◽  
Kunihiko Koshiba ◽  
...  

Endothelial function remains chronically abnormal after vascular injury associated with coronary intervention. The long-term effects of drug-eluting stent (DES) on endothelial function are not known. We evaluated the endothelial-dependent vasomotor function and local release of pentraxin3 (PTX3) as a local inflammatory marker in nonrestenotic coronary arteries more than six months following DES and bare metal stent (BMS) implantation. Fifty-two patients treated six months earlier with a coronary stenting for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Twenty patients had been stented with BMS, and 32 had been with DES. Changes in diameter at distal site of the stented LAD in response to intracoronary acetylcholine (Ach) infusions (1,3,10,30 μg/min) were assessed by quantitative angiography. At the completion of the protocol, a 2mg bolus of isosorbide dinitrate (ISDN) was injected into the LAD. We also measured serum PTX3 levels sampled in coronary sinus (CS) and sinus of Valsalva (V). Results: The two groups had similar risk factors for endothelial dysfunction. The mean percent change in the diameter of the stented LAD by Ach injection was significantly more in the DES group than in the BMS group (−38.9±6.1 vs. −19.2±6.7 %, p<0.01). There was no significant difference in maximal dilation achieved by ISDN infusion between the two groups (34.6±6.6 vs. 31.2±4.6 %, NS). The translesional PTX3 gradient (CS-PTX3 minus V-PTX3) was higher in the DES group than in the BMS group (+0.11±0.05 vs. −0.01±0.05 ng/ml, p<0.01). More severe endothelial dysfunction was observed long term after DES implantation as compared to BMS. These findings were associated with an increased local inflammatory response to DES stenting.


2014 ◽  
Vol 13 (5) ◽  
pp. 169-178
Author(s):  
I. A. Khripun ◽  
Z. R. Gtisova ◽  
H. S. Ibishev ◽  
A. S. Sultanmuradova ◽  
S. V. Vorobiev ◽  
...  

Endothelial dysfunction is an early marker for the development and progression of cardiovascular diseases. Scientific studies in recent years have shown the necessity to study the endothelial function in different groups of patients in clinical practice. This article is focused on the possibilities and perspectives for clinical use of laboratory and instrumental methods for the study of endothelial function. One of the factors causing the development of vascular disease in men is testosterone deficiency. The review highlights the most important mechanisms of action of sex hormones on the vascular endothelium and its function in men. The data about the effects of hormone replacement therapy with testosterone on endothelial function in patients with late onset hypogonadism were critically analyzed.


2020 ◽  
Vol 27 (7) ◽  
pp. 1052-1080 ◽  
Author(s):  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Vasiliki Tsigkou ◽  
Evanthia Bletsa ◽  
Maria-Evi Panoilia ◽  
...  

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.


2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3&#039;, 5&#039;-monophosphate (cGMP) and adenosine 3&#039;, 5&#039;-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.


2020 ◽  
Vol 26 (32) ◽  
pp. 3955-3972
Author(s):  
Ecem Kaya-Sezginer ◽  
Serap Gur

Background: Erectile dysfunction (ED) is an evolving health problem in the aging male population. Chronic low-grade inflammation is a critical component of ED pathogenesis and a probable intermediate stage of endothelial dysfunction, especially in metabolic diseases, with the inclusion of obesity, metabolic syndrome, and diabetes. Objective: This review will present an overview of preclinical and clinical data regarding common inflammatory mechanisms involved in the pathogenesis of ED associated with metabolic diseases and the effect of antiinflammatory drugs on ED. Methods: A literature search of existing pre-clinical and clinical studies was performed on databases [Pubmed (MEDLINE), Scopus, and Embase] from January 2000 to October 2019. Results: Low-grade inflammation is a possible pathological role in endothelial dysfunction as a consequence of ED and other related metabolic diseases. Increased inflammation and endothelial/prothrombotic markers can be associated with the presence and degree of ED. Pharmacological therapy and modification of lifestyle and risk factors may have a significant role in the recovery of erectile response through reduction of inflammatory marker levels. Conclusion: Inflammation is the least common denominator in the pathology of ED and metabolic disorders. The inflammatory process of ED includes a shift in the complex interactions of cytokines, chemokines, and adhesion molecules. These data have established that anti-inflammatory agents could be used as a therapeutic opportunity in the prevention and treatment of ED. Further research on inflammation-related mechanisms underlying ED and the effect of therapeutic strategies aimed at reducing inflammation is required for a better understanding of the pathogenesis and successful management of ED.


2021 ◽  
pp. 1-9
Author(s):  
Narges Ghorbani Bavani ◽  
Parvane Saneei ◽  
Ammar Hassanzadeh Keshteli ◽  
Ahmadreza Yazdannik ◽  
Ebrahim Falahi ◽  
...  

Abstract Objective: We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. Design: A cross-sectional study. Setting: Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Participants: Iranian female nurses (n 345) selected by a multistage cluster random sampling method. Results: The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Conclusions: Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.


2021 ◽  
Vol 22 (1) ◽  
pp. 147032032199949
Author(s):  
Miaomiao Sang ◽  
Yu Fu ◽  
Chenmin Wei ◽  
Jing Yang ◽  
Xueting Qiu ◽  
...  

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.


2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.


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