Endotelová dysfunkcia spojená s funkčnou poruchou dilatácie ciev je jedno z prvých štádií aterosklerózy detekovateľných ešte pred vývinom morfologických cievnych zmien a predstavuje závažnú komplikáciu u pacientov s dyslipidémiou. Význam jej diagnostiky spočíva najmä v tom, že je dobrým prediktorom kardiovaskulárnych udalostí nezávisle na prítomnosti klasických kardiovaskulárnych rizikových faktorov napriek tomu, že do klinickej praxe nebola doteraz zavedená. Endotelová dysfunkcia je prítomná u pacientov s rôznymi druhmi dyslipidémií, pričom existujú viaceré dôkazy o možnosti jej ovplyvnenia prostredníctvom farmakoterapie. Mnohé hypolipidemiká majú endotelovo-protektívne vlastnosti, ktoré pravdepodobne nie sú len výsledkom ich hypolipidemického účinku, ale zároveň perspektívnymi prostriedkami pre zníženie kardiovaskulárneho rizika u dyslipidemických pacientov. Predkladaný článok sa venuje endotelovej dysfunkcii a možnostiam jej farmakologického ovplyvnenia. Cieľom je vytvoriť stručný prehľad hypolipidemík s potenciálom zmierniť alebo zvrátiť endotelovú dysfunkciu a diskutovať potenciálne mechanizmy ich endotelovo-protektívneho účinku na základe výsledkov doteraz publikovaných experimentálnych a klinických štúdií.
Endothelial dysfunction, the term commonly describing the impairment in its vasodilatory capacity, is the first stage of atherosclerosis which can be detected before the first morphological changes of vessels occur. It is a good predictor of cardiovascular events, independent of the presence of traditional cardiovascular risk factors. Despite this, its use has not reached widespread clinical acceptance. Endothelial dysfunction is present in patients with various types of dyslipidemia and there is a growing body of evidence that it can be reversed by various pharmacological approaches. Many hypolipidemics have been described to exert endothelium-protective effects independent of their lipid-lowering properties, which is indicative of the lowering of cardiovascular risk in dyslipidemic patients. This review article aims to discuss endothelial dysfunction, its pathophysiology, as well as hypolipidemics with a potential to reverse endothelial dysfunction and potential mechanisms of their endothelium-protective effects.
- Klíčová slova
- endoteliální dysfunkce,
- MeSH
- ateroskleróza etiologie MeSH
- cévní endotel * patofyziologie účinky léků MeSH
- deriváty kyseliny fibrové farmakologie terapeutické užití MeSH
- dyslipidemie etiologie farmakoterapie MeSH
- ezetimib farmakologie terapeutické užití MeSH
- hypolipidemika * farmakologie terapeutické užití MeSH
- kardiovaskulární nemoci etiologie prevence a kontrola MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- statiny farmakologie terapeutické užití MeSH
- vazodilatace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg(-1). SLX was administered i.p., at dose 100 IU.kg(-1) daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO(2)(S(3))], [QO(2)(S(4))] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function.
- MeSH
- cévní endotel účinky léků fyziologie MeSH
- experimentální diabetes mellitus farmakoterapie metabolismus patologie MeSH
- glykosaminoglykany farmakologie terapeutické užití MeSH
- jaterní mitochondrie účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- orgánové kultury - kultivační techniky MeSH
- potkani Wistar MeSH
- vazodilatancia farmakologie terapeutické užití MeSH
- vazokonstriktory farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The impact of air pollution exposure on the level of total DNA adducts in human white blood cells (WBCs) was evaluated in two populations in the Czech Republic and compared to the exposure-DNA adduct relationship in other populations in the US and China in human lung cells and rodent lung tissue. The human populations examined were exposed to respirable particles (< 2.5 microm) (PM2.5) in urban, rural, and occupational settings where the particles originated from coal and petroleum fuel combustion, coke production, and other coal-tar aerosols (e.g., used in aluminum production). These particles contain carcinogenic polycyclic aromatic hydrocarbons (PAHs) that are known to form DNA adducts through covalent binding. Personal exposure to PM2.5 and PAHs were measured prior to collection of blood samples for DNA adduct analysis by 32P-postlabeling. Coke oven workers (n = 76), in 10 job categories on the top and side of a coke oven in Ostrava, CZ, were studied and compared to a different population exposed to environmental levels of PAHs from air pollution in Teplice, CZ. Personal exposures to airborne particles ranged from < 1 to more than 15,000 microg/m3 and carcinogenic PAHs exposure ranged from < 5 to > 200,000 ng/m3. At low to moderate environmental exposures to carcinogenic PAHs, DNA adduct levels in the WBCs were significantly correlated with exposure. However, at the higher occupational levels found on the coke oven, the exposure-DNA adduct relationship became non-linear. Under these high exposure conditions, the relative DNA adduct level per unit of exposure (DNA-binding potency) was significantly lower than measured at environmental exposures. This finding is consistent with observations in lung cells from bronchoalveolar lavage of humans exposed to a wide range of PAH. This same high exposure-dose non-linearity was also observed in lung DNA from rats exposed by inhalation to a coal-tar pitch aerosol. DNA adduct levels in all these cases show evidence of a form of non-linearity at high doses that has been described by Lutz (W.K. Lutz, Dose-response relationship and low dose extrapolation in chemical carcinogenesis, Carcinogenesis, 11 (1990) 1243-1247) as a superlinear dose response. This superlinear response may be due to saturation of metabolic activation enzymes, induction of either DNA repair processes or detoxification enzymes, or other mechanisms. Regardless of the mechanism, this decrease in the DNA-binding potency at moderate to high doses of PAH has important implications for dose-response extrapolation in risk assessment.
- MeSH
- adukty DNA krev MeSH
- benzopyren analýza toxicita MeSH
- dehet uhelný škodlivé účinky MeSH
- endonukleasy metabolismus MeSH
- karcinogeny škodlivé účinky MeSH
- kouření MeSH
- krysa rodu rattus MeSH
- látky znečišťující vzduch v pracovním prostředí škodlivé účinky MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- leukocyty chemie MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- polycyklické aromatické uhlovodíky škodlivé účinky MeSH
- potkani Wistar MeSH
- pracovní expozice MeSH
- radioizotopy fosforu metabolismus MeSH
- vystavení vlivu životního prostředí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- bakteriofág lambda účinky léků MeSH
- hydroxylaminy farmakologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
