Regulation of nitric oxide production in hypothyroidism

Hypothyroidism is a common endocrine disorder that predominantly occurs in females. It is associated with an increased risk of cardiovascular diseases (CVD), but the molecular mechanism is not known. Disturbance in lipid metabolism, the regulation of oxidative stress, and inflammation characterize the progression of subclinical hypothyroidism. The initiation and progression of endothelial dysfunction also exhibit these changes, which is the initial step in developing CVD. Animal and human studies highlight the critical role of nitric oxide (NO) as a reliable biomarker for cardiovascular risk in subclinical and clinical hypothyroidism. In this review, we summarize the recent literature findings associated with NO production by the thyroid hormones in both physiological and pathophysiological conditions. We also discuss the levothyroxine treatment effect on serum NO levels in hypothyroid patients. © 2020 The Author

The role of L-Arginine in cardiovascular system

Esencijalna aminokiselina, L-Arginin (L-Arg) ima veoma važnu ulogu u kardiovaskularnom sistemu. Podaci iz literature pokazuju da je L-Arg jedini supstrat za produkciju azot-monoksida (NO), preko koga L-Arg i ostvaruje svoje efekte na kardiovaskularni sistem. Kao slobodni radikal, NO se sintetiše u svim ćelijama sisara od L-Arg uz aktivnost enzima NO sintaze (NOS). U stanjima hipertenzije, dijabetesa, hiperholesterolemije i vaskularne inflamacije dolazi do poremećaja metaboličkog puta sinteze NO od L-Arg, što sve zajedno dovodi do oštećenja krvnih sudova. Kliničke studije ukazuju da L-Arg može imati efekte na trombocite, proces koagulacije kao i na fibrinolitički sistem. U okviru ovog preglednog članka sumirani su najnoviji podaci iz literature koji sugerišu da bi L-Arg mogao biti jedan od bitnih terapeutskih molekula u poboljšanju lečenja kardiovaskularnih poremećaja.The essential amino acid, L-Arginine (L-Arg) has an important role in the cardiovascular system. Literature data show that L-Arg is the only substrate for the production of nitric oxide (NO), from which L-Arg develops its effects on the cardiovascular system. As a free radical, NO is synthesized in all mammal cells by L-Arg with the activity of NO synthase (NOS). In the states of hypertension, diabetes, hypercholesterolemia and vascular inflammation, a disorder occurs in the metabolic pathway of the synthesis of NO from L-Arg which all together bring alterations to blood vessels. Clinical studies show that L-Arg has an effect on thrombocytes, the process of coagulation and the fibrolytic system. All the new data summarized in this review suggest that L-Arg could be one of important therapeutic molecules for improving cardiovascular disorders

The role of the nitric oxide synthases in brain ischemia during carotid endarterectomy

Prema podacima Svetske zdravstvene organizacije, 15 miliona ljudi godišnje doživi moždani udar. Najčešći uzročnik moždanog udara je ishemija mozga, koja se dešava u skoro 85% slučajeva. Moždana ishemija izazvana tromboembolijskim događajima definiše se kao trajno ili prolazno smanjenje cirkulacije krvi, što za posledicu ima nedostatak kiseonika, glukoze i ostalih važnih nutritijenata, dovodeći postepeno do metaboličkih promena i apoptoze ćelija. Tokom operativnih zahvata kao što je karotidna endarterektomija (CEA) može doći do hipoksično-ishemičnog stanja mozga ili akutne ishemije mozga (ABI), kao i do samog moždanog udara. Glavni uzrok ABI u toku CEA je cerebralna hipoperfuzija koja je uzrokovana klemovanjem karotidne arterije, pri čemu dolazi do hipoksije, što može predstavljati jedan od okidača za niz fizioloških odgovora organizma, među kojima je oslobađanje različitih medijatora inflamacije. Jedan od medijatora inflamacije je i azot monoksid (NO), slobodni radikal koji pored mnogobrojnih fizioloških efekata ima važnu ulogu i u samom imunom odgovoru organizma. Međutim, NO može biti veoma štetan i svojim delovanjem dovesti do oštećenja ćelija i tkiva. Nedostatak podataka u literaturi o ulozi endotelne NOS (eNOS) i inducibilne NOS (iNOS) tokom CEA, kao i mehanizama njihove regulacije u stanjima ishemije, ukazuju na pravac kojim treba da se usmere buduća istraživanja. Poznavanje molekularnih mehanizama regulacije aktivnosti i ekspresije iNOS, svakako će pomoći razvoju novih terapijskih strategija u tretmanu štetnih efekata produkcije slobodnih radikala, pre svega nekontrolisane produkcije NO.According to the World Health Organization, 15 million people per year are affected by stroke. The most common cause of stroke is brain ischemia, which occurs in almost 85% of cases. Ischemia caused by thromboembolism is defined as permanently or temporarily decreased blood flow which prevents an adequate delivery of oxygen, glucose and other important nutrients, leading progressively to metabolic changes and cell apoptosis. Carotid endarterectomy (CEA) can cause hypoxic - ischemic states of the brain or acute brain ischemia (ABI) leading eventually to stroke. The main cause of ABI as a result of CEA is cerebral hypoperfusion caused by clamping of carotid arteries, when hypoxia occurs.. Hypoxia per se is one of the triggers of complex physiological responses in the body, including the release of various mediators of inflammation. One of these inflammatory mediators is nitric oxide (NO), a free radical which has numerous physiological effects and also plays an important role in the immune response of the organism. However, NO may be very harmful and cause cell and tissue damage. The lack of literature data on the role of endothelial NOS (eNOS) and inducible NOS (iNOS) during CEA, as well as the mechanisms of their regulation in ischemic conditions, suggest that intensifying future research in this field is very important. An insight into molecular mechanisms of iNOS activity and expression regulation will certainly help to develop new therapeutic strategies for treating harmful effects of free radicals, especially uncontrolled production of NO

Genetic Markers for Coronary Artery Disease

Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

The association of ACE I/D gene polymorphism with severe carotid atherosclerosis in patients undergoing carotid endarterectomy

Introduction: The ACE I/D polymorphism was mostly investigated in association with intima-media thickness, rarely with severe atherosclerotic phenotype. Materials and methods: We investigated the association of I/D polymorphism with severe carotid atherosclerosis (CA) (stenosis GT 70%) in asymptomatic and symptomatic patients undergoing carotid endarterectomy. The 504 patients subjected to endarterectomy and 492 healthy controls from a population in Serbia were investigated as a case-control study. Results: The univariate logistic regression analysis revealed ACE DD as a significant risk factor for severe CA (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.0-1.7, p = 0.04). After adjustment for the common risk factors (age, hypertension, smoking, and HDL) ACE was no longer significant. However, we found a significant independent influence of DD genotype on plaque presence in a normotensive subgroup of patients (OR 1.8, CI 1.2-3.0, p = 0.01, corrected for multiple testing). In symptomatic patients D allele carriers were significantly more frequent compared with asymptomatic patients (OR 1.6 CI 1.0-2.6, p = 0.05). Conclusions: Our data suggests that ACE I/D is not an independent risk factor for severe CA. On the other hand, a significant independent genetic influence of ACE I/D appeared in normotensive and symptomatic patients with severe CA. This should be considered in further research toward resolving the complex genetic background of severe CA phenotype

Link Between Oxidative Stress and Acute Brain Ischemia

The pathogenesis of acute brain ischemia (ABI) is highly complex and involves multiple mechanisms including free radical generation. Imbalance between the cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress. Oxidative stress is one of the mechanisms contributing to neuronal damage, potentially induced through the ABI. Through interactions with a large number of molecules, reactive oxygen species may irreversibly destroy or alter the function of the cellular lipids, proteins, and nucleic acids and initiate cell signaling pathways after cerebral ischemia. Future investigations should focus on the understanding of oxidative stress mechanisms and neuro-protection in order to discover new treatment targets

Changes in Hypothalamus-Pituitary-Adrenal Axis Following Transient Ischemic Attack

Acute brain ischemia caused by transient ischemic attack initiates a complex sequence of events in the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis which may ultimately culminate in neuronal and cell damage. The brain is highly susceptible to ischemia and in response to stress shows changes in morphology and chemistry that are largely reversible. These responses are known to modify the function of the HPA axis, but their mechanisms are not yet clear. Duration and size of the HPA axis activation are regulated by corticotropin-releasing hormone, vasopressin (AVP), and glucocorticoids, including cortisol. Numerous studies suggest that activation of these hormones following brain ischemia can result in neurohormonal dysfunction that can exacerbate long-term prognosis following stroke. These studies represent evidence that changes in the HPA axis play an important role in brain ischemia

Inflammation as a Marker for the Prediction of Internal Carotid Artery Restenosis Following Eversion Endarterectomy-Evidence From Clinical Studies

The role of inflammation is well established in the pathogenesis of atherosclerosis and an increased level of circulating inflammatory markers may predict the future risk of atherosclerosis progression and plaque rupture. C-reactive protein (CRP) identification by hypersensitive methods (high-sensitivity CRP [hsCRP]) has become a clinical and laboratory inflammation marker. Carotid endarterectomy (CEA) is a well-established procedure for carotid stenosis treatment which can reduce stroke rate. Internal carotid artery (ICA) restenosis reduction may be prevented by the anti-inflammatory effect of statins. This review considers the recent findings on the presence of hsCRP and C3 complement concentration and inflammatory plaque composition as well as their effects on ICA restenosis rate, following eversion CEA with emphasis on human studies