Myocardial Perfusion and Coronary Physiology Assessment of Microvascular Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation-Rationale and Design.

The prevalence of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is 30-68%. Nevertheless, there is still not enough evidence to use invasive assessment of lesion severity, because the hemodynamic milieu of AS may impact the fractional flow reserve (FFR) and non-hyperemic indices. Therefore, the aim of the study is two-fold. First, to measure acute and long-term changes of FFR, index of microvascular resistance (IMR), and coronary flow reserve (CFR) in patients undergoing TAVI procedure. Second, to compare the diagnostic accuracy of intracoronary indices with myocardial perfusion measured by cadmium-zinc-telluride single-photon emission tomography (CZT-SPECT) and find cut-off values defining significant stenosis. We plan to enroll 40 patients eligible for TAVI with intermediate stenosis (30-70%) in the left anterior descending (LAD) coronary artery. In each patient FFR, CFR, and IMR will be measured in addition to myocardial blood flow calculated by CZT-SPECT before and either immediately after TAVI (acute cohort) or in 6 months (late cohort) after the procedure. FFR, CFR, and IMR will be matched with the results of myocardial perfusion measured by CZT-SPECT in the area of LAD. As a result, cut-off values of FFR, CFR, and IMR defining the decreased blood flow will be found.

Bioactive Sphingolipids, Complement Cascade, and Free Hemoglobin Levels in Stable Coronary Artery Disease and Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) and coronary artery bypass graft (CABG) surgery are associated with a pathogen-free inflammatory response (sterile inflammation). Complement cascade (CC) and bioactive sphingolipids (BS) are postulated to be involved in this process. AIM: The aim of this study was to evaluate plasma levels of CC cleavage fragments (C3a, C5a, and C5b9), sphingosine (SP), sphingosine-1-phosphate (S1P), and free hemoglobin (fHb) in AMI patients treated with primary percutaneous coronary intervention (pPCI) and stable coronary artery disease (SCAD) undergoing CABG. PATIENTS AND METHODS: The study enrolled 37 subjects (27 male) including 22 AMI patients, 7 CABG patients, and 8 healthy individuals as the control group (CTRL). In the AMI group, blood samples were collected at 5 time points (admission to hospital, 6, 12, 24, and 48 hours post pPCI) and 4 time points in the CABG group (6, 12, 24, and 48 hours post operation). SP and S1P concentrations were measured by high-performance liquid chromatography (HPLC). Analysis of C3a, C5a, and C5b9 levels was carried out using high-sensitivity ELISA and free hemoglobin by spectrophotometry. RESULTS: The plasma levels of CC cleavage fragments (C3a and C5b9) were significantly higher, while those of SP and S1P were lower in patients undergoing CABG surgery in comparison to the AMI group. In both groups, levels of CC factors showed no significant changes within 48 hours of follow-up. Conversely, SP and S1P levels gradually decreased throughout 48 hours in the AMI group but remained stable after CABG. Moreover, the fHb concentration was significantly higher after 24 and 48 hours post pPCI compared to the corresponding postoperative time points. Additionally, the fHb concentrations increased between 12 and 48 hours after PCI in patients with AMI. CONCLUSIONS: Inflammatory response after AMI and CABG differed regarding the release of sphingolipids, free hemoglobin, and complement cascade cleavage fragments.

Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate.

The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged. In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential. Thus, the BM stem cell compartment hierarchy needs to be revisited. These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names. As reported, murine VSELs have some pluripotent stem cell characteristics. Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM. Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2-H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues. In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration. Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies. VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation.

Circulating microRNAs (miR-423-5p, miR-208a and miR-1) in acute myocardial infarction and stable coronary heart disease.

AIM: The microRNAs (miRs) are small non-coding RNAs which regulate expression of multiple genes involved in atherogenesis. MicroRNA are also present in circulation. The aims of this study were: 1) assessment of expression level of miR-1, miR-208a and miR-423-5p in plasma in patients with STEMI, stable CAD and healthy individuals; 2) evaluation of correlation between plasma miRs and left ventricle ejection fraction, end- systolic and end-diastolic diameters and troponin release in patients with STEMI. METHODS: Study group consisted of 26 patients: 1) acute MI group (N.=17); 2) stable CAD group (N.=4); and 3) subjects with no history of CAD (control group, N.=5). Expression of miR-423-5p, miR-208 and miR-1 was measured in plasma before PCI, 6, 12 and 24 hours later. Expression level ofmiRs was measured using TaqMan® MicroRNA Assays. Expression was assessed by Pfaffl method, and miR-39 was used for normalization of the results. RESULTS: In stable CAD in comparison to control group the expression level of miR-1, miR-208a and miR-423-5p did not show significant differences. Also there was no significant increase of number of miR copies at 6, 12 and 24 hours after PCI. There was a significantly higher number of miR-423-5p copies in patients with acute MI before the pPCI. After 6, 12 and 24 hours post-procedure the expression level was similar to the control group and significantly lower than the baseline level. Conversely, the expression level of miR-1 and miR-208a were not significantly different than in the control group. In patients with acute MI there were no significant correlations between the expression level of miRs and any of the echocardiographic parameters of LV as well as level of troponin I at any time-point of the follow-up. CONCLUSION: Early in acute myocardial infarction the expression of miR-423-5p in plasma is significantly increased with subsequent normalization within 6 hours. Potentially it is an early marker of myocardial necrosis.

Circulating endothelial progenitor cells are inversely correlated with in-stent restenosis in patients with non-ST-segment elevation acute coronary syndromes treated with EPC-capture stents (JACK-EPC trial).

AIM: Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). METHODS: Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. INCLUSION CRITERIA: de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. EXCLUSION CRITERIA: diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. RESULTS: Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/µL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). CONCLUSION: Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).

Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?

Although regenerative medicine is searching for pluripotent stem cells that could be employed for therapy, various types of more differentiated adult stem and progenitor cells are in meantime being employed in clinical trials to regenerate damaged organs (for example, heart, kidney or neural tissues). It is striking that, for a variety of these cells, the currently observed final outcomes of cellular therapies are often similar. This fact and the lack of convincing documentation for donor-recipient chimerism in treated tissues in most of the studies indicates that a mechanism other than transdifferentiation of cells infused systemically into peripheral blood or injected directly into damaged organs may have an important role. In this review, we will discuss the role of (i) growth factors, cytokines, chemokines and bioactive lipids and (ii) microvesicles (MVs) released from cells employed as cellular therapeutics in regenerative medicine. In particular, stem cells are a rich source of these soluble factors and MVs released from their surface may deliver RNA and microRNA into damaged organs. Based on these phenomena, we suggest that paracrine effects make major contributions in most of the currently reported positive results in clinical trials employing adult stem cells. We will also present possibilities for how these paracrine mechanisms could be exploited in regenerative medicine to achieve better therapeutic outcomes. This approach may yield critical improvements in current cell therapies before true pluripotent stem cells isolated in sufficient quantities from adult tissues and successfully expanded ex vivo will be employed in the clinic.

Mobilization of stem and progenitor cells in cardiovascular diseases.

Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the peripheral blood, including hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, circulating angiogenic cells and pluripotent very small embryonic-like cells; however, the contribution of circulating cells to the myocardial and endothelial repair is still unknown. The number and function of these cells is impaired in patients with diabetes and other cardiovascular risk factors, but can be improved by physical exercise and use of statins. The mobilization of SPCs in acute coronary syndromes and stable coronary artery disease seems to predict the clinical outcomes in selected groups of patients. Interpretation of the findings has to incorporate other factors that modulate the process of mobilization, such as coexisting diseases, age and medications. This review discusses the mobilization of SPCs in acute ischemia (MI, stroke), as well as in stable cardiovascular disease, and highlights the possibility of using the SPC as a marker of cardiovascular risk.

Mobilization of very small embryonic-like stem cells in acute coronary syndromes and stroke.

The bone marrow (BM) niche contains small heterogenous populations of cells which may contribute to cardiac and endothelial repair, including committed lineages [endothelial progenitor cells (EPCs), multipotent mesenchymal stromal cells (MSCs) and more primitive very small embryonic-like cells (VSELs) expressing pluripotent stem cell (PSC) markers (Oct-4, Nanog, SSEA-1)]. VSELs are present in BM, peripheral blood and some solid organs in mice and were recently identified in peripheral blood in patients with acute coronary syndromes and stroke. VSELs can be expanded in vitro and differentiated into cells from all three germ layers. This population of cells displays the morphology of primitive PSC (small size, open type chromatin, large nucleus, narrow rim of cytoplasm) and express PSC markers. The isolation of human VSELs is based on their size and presence of several surface markers (CXCR4, CD133, CD34) and lack of markers of hematopoietic lineage (lin, CD45). In acute myocardial infarction and ischemic stroke VSELs are rapidly mobilized into peripheral blood, and express increased levels of PSC markers as well as early cardiac (GATA-4, Nkx2.5/Csx), neural (GFAP, nestin, beta-III-tubulin, Olig1, Olig2, Sox2, Musashi) and endothelial lineage markers (VE-cadherin, von Willebrand factor). The number of VSELs mobilized in acute myocardial infarction is inversely correlated with left ventricular ejection fraction and the release of cardiac necrosis markers. Mobilization of these cells is also reduced in patients with diabetes and in the elderly. BM-derived VSELs were expanded and after cardiogenic pre-differentiation injected intramyocardially in mice models of myocardial infarction leading to improved left ventricular contractility. VSELs are probably progeny of epiblast cells which migrated to the BM and developing organs during embryonic development. The cells are present in a quiescent state in the adult BM and solid organs and might serve as a reserve pool of resident stem cells. VSELs are promising candidates for further pre-clinical and clinical studies on cellular cardiovascular therapy.

Innate immunity as orchestrator of stem cell mobilization.

Hematopoietic stem and progenitor cells (HSPCs), as well as other types of stem cells, circulate under steady-state conditions at detectable levels in peripheral blood (PB), with their numbers increasing in response to stress, inflammation and tissue/organ injury. This mobilization process may be envisioned as a danger-sensing response mechanism triggered by hypoxia or mechanical or infection-induced tissue damage that recruits into PB different types of stem cells that have a role in immune surveillance and organ/tissue regeneration. Mobilization is also significantly enhanced by the administration of pharmacological agents, which has been exploited in hematological transplantology as a means to obtain HSPCs for hematopoietic reconstitution. In this review we will present mounting evidence that innate immunity orchestrates this evolutionarily conserved mechanism of HSPC mobilization.

Circulating progenitor cells in stable coronary heart disease and acute coronary syndromes: relevant reparatory mechanism?

Bone marrow-derived cells which may be involved in cardiac repair/regeneration after ischaemic injury must undergo mobilisation into peripheral blood with subsequent homing and engraftment into the target organ. Mobilisation of the heterogeneous population of stem/progenitor cells in endothelial injury or myocardial ischaemia has been described recently. The number of circulating stem/progenitor cells reflects the endothelial damage, and turnover may be a surrogate marker reflecting the burden of cardiovascular risk factors and prognostic markers in stable coronary heart disease and acute coronary syndromes. Acute coronary syndromes are associated with increased levels of inflammatory and haematopoietic cytokines which, in turn, can mobilise progenitor cells from the bone marrow. Myocardial infarction increases the number of endothelial progenitor cells and other less well-defined subpopulations, such as CD34/c-kit(+) and CD34/CXCR4(+) cells, which may take part in cardiac repair after ischaemic injury. Data on mobilisation of stem/progenitor cells in acute coronary syndromes are summarised here. Cell types, mechanisms of mobilisation, homing and engraftment are discussed and their relevance to clinical outcomes.

A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues.

Accumulating evidence demonstrates that adult tissues contain a population of stem cells that express early developmental markers such as stage-specific embryonic antigen and transcription factors Oct-4 and Nanog. These are the markers characteristic for embryonic stem cells, epiblast stem cells and primordial germ cells. The presence of these stem cells in adult tissues including bone marrow, epidermis, bronchial epithelium, myocardium, pancreas and testes supports the concept that adult tissues contain some population of pluripotent stem cells that is deposited in embryogenesis during early gastrulation. In this review we will discuss these data and present a hypothesis that these cells could be direct descendants of the germ lineage. The germ lineage in order to pass genes on to the next generations creates soma and thus becomes a 'mother lineage' for all somatic cell lineages present in the adult body.

Morphological and molecular characterization of novel population of CXCR4+ SSEA-4+ Oct-4+ very small embryonic-like cells purified from human cord blood: preliminary report.

Recently, we purified from adult murine bone marrow (BM) a population of CXCR4(+), Oct-4(+) SSEA-1(+), Sca-1(+) lin(-) CD45(-) very small embryonic-like (VSEL) stem cells and hypothesized that similar cells could be also present in human cord blood (CB). Here, we report that by employing a novel two-step isolation procedure -- removal of erythrocytes by hypotonic lysis combined with multiparameter sorting -- we could isolate from CB a population of human cells that are similar to murine BM-derived VSELs, described previously by us. These CB-isolated VSELs (CB-VSEL) are very small (3-5 micro m) and highly enriched in a population of CXCR4(+)AC133(+)CD34(+)lin(-) CD45(-) CB mononuclear cells, possess large nuclei containing unorganized euchromatin and express nuclear embryonic transcription factors Oct-4 and Nanog and surface embryonic antigen SSEA-4. Further studies are needed to see if human CB-isolated VSELs similar to their murine BM-derived counterparts are endowed with pluripotent stem cell properties.

The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis.

Proper response of normal stem cells (NSC) to motomorphogens and chemoattractants plays a pivotal role in organ development and renewal/regeneration of damaged tissues. Similar chemoattractants may also regulate metastasis of cancer stem cells (CSC). Growing experimental evidence indicates that both NSC and CSC express G-protein-coupled seven-transmembrane span receptor CXCR4 and respond to its specific ligand alpha-chemokine stromal derived factor-1 (SDF-1), which is expressed by stroma cells from different tissues. In addition, a population of very small embryonic-like (VSEL) stem cells that express CXCR4 and respond robustly to an SDF-1 gradient was recently identified in adult tissues. VSELs express several markers of embryonic and primordial germ cells. It is proposed that these cells are deposited early in the development as a dormant pool of embryonic/pluripotent NSC. Expression of both CXCR4 and SDF-1 is upregulated in response to tissue hypoxia and damage signal attracting circulating NSC and CSC. Thus, pharmacological modulation of the SDF-1-CXCR4 axis may lead to the development of new therapeutic strategies to enhance mobilization of CXCR4+ NSC and their homing to damaged organs as well as inhibition of the metastasis of CXCR4+ cancer cells.

Plasma levels of von willebrand factor, endothelin-1, prostacyclin and thromboxane in children from families with high risk of premature coronary artery disease.

The aim of the study was to assess the plasma levels of endothelial injury markers in children from families with high risk of premature coronary heart disease (CHD) without other common CHD risk factors (hyperlipidaemia, obesity, hypertension, low physical activity). The study comprised 48 children, including 24 children from high-risk families (HR), according to the NCEP (National Cholesterol Education Programme) criteria: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). The control group included 24 healthy children with no familial history of cardiovascular disease. All the children were normolipidaemic according to the NCEP and the European Atherosclerosis Society criteria for children aged 2-19 years. In the HR group, the concentration of vWf was significantly elevated in comparison to that in the control group (p<0.0001). Plasma concentrations of ET-1 and TxB2 did not differ significantly between the HR group and the controls. Plasma concentrations of the 6-ketoPGF1alpha in the HR group and in the respective age and gender HR subgroups were significantly lower compared with those of the control group (p<0.00005). Concentration of vWf in the HR group was negatively correlated with the concentration of 6-ketoPGF1alpha (r = -0.47; p<0.05) and positively correlated with TxB2 (r=0.39; p<0.01). In a logistic regression analysis, we found that the 6-ketoPGF1alpha concentration in the lower quartile (< 16.1 pmol/L) was associated with a 3.4-fold odds of inclusion in the high-risk group versus the upper quartile (>23.0 pmol/L).

Soluble ICAM-1, VCAM-1 and E-selectin in children from families with high risk of atherosclerosis.

The genetic predisposition for cardiovascular disease seems to play an important role in atherogenesis. Atherosclerosis, which can be clinically asymptomatic for many years, begins early in life. Therefore finding markers of early atherosclerotic process would be of great importance for screening and early treatment of these children. As the result of endothelial dysfunction, the adhesion molecules (VCAM-1, ICAM-1, ELAM) are overexpressed. These molecules are shed from the surface and can be measured, as soluble forms in serum. Therefore they can be regarded as early markers of atherosclerosis. The aim of the study was to measure the serum levels of soluble adhesion molecules ELAM, ICAM-1, VCAM-1 and plasma lipid profile--total (TC), LDL (LDL-C) and HDL-cholesterol (HDL-C) and triglycerides (TG) in children from families of high risk for cardiovascular diseases. Forty-eight children were studied, 24 children from high risk families, according to NCEP definition: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). Twenty-four healthy children without familial history of cardiovascular disease were used as the control. Children of either group did not have any metabolic diseases. The concentration of sELAM, sICAM-1 and sVCAM-1 were assessed using ELISA kits. Soluble ICAM-1 level was significantly higher in high risk group in comparison to control (p<0.02). The soluble VCAM-1 and ELAM levels did not differ significantly between the groups. There were no changes in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the groups. In normolipidemic children from families with high risk for atherosclerosis the soluble ICAM-1 levels are significantly higher as compared to control.

The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.

Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.

[HMG-CoA reductase inhibitors in prevention of cardiovascular diseases: new mechanisms, aspects and trials]. / Inhibitory reduktazy HMG-CoA w prewencji chorób ukladu krazenia--nowe mechanizmy, aspekty, programy.

Use of lipid-lowering drugs in both primary and secondary prevention of cardiovascular disease (CVD) decreases significantly risk of myocardial infarction, stroke, incidence of cardiovascular events, reduces the cardiovascular mortality and morbidity as well as total mortality. HMG-CoA reductase inhibitors (statins) are most potent cholesterol-lowering drugs. Statins act by inhibition of HMG-CoA reductase activity, a rate--limiting step in synthesis of cholesterol and important metabolites of mevalonate--isoprenoids. The mechanisms by which favourable antiatherogenic actions of statins occur are complex. Statins inhibit proliferation and migration of vascular smooth muscle cells, reduce free-radicals generation and LDL modification, lower Lp(a) concentration, inhibit macrophage-derived foam cells accumulation and inhibit activation of platelets, thromboxane and PAI-1 synthesis. Use of statins in the therapy of hypercholesterolemia is presently recommended by NCEP, especially in high-risk groups (diabetes, post-CABG and PTCA, kidney and heart transplantation). Nevertheless, patients with CAD and moderately elevated LDL-C levels also benefit from the treatment with statins. Because of high costs of the therapy, statins of most favourable pharmacoeconomic profile should be used.

The influence of angiotensin converting enzyme inhibitors on lipid peroxidation in sera and aorta of rabbits in diet-induced hypercholesterolemia.

In hypercholesterolemia increased lipid and lipoprotein peroxidation occurs. The renin-angiotensin system plays an important role in atherogenesis. Angiotensin II induces smooth muscle cells proliferation and stimulates oxidation of LDL particles and foam cell accumulation. Inhibition of ang II production leads to decrease in lipid peroxide production. The aim of this study was to assess the lipid peroxidation expressed as concentration of thiobarbituric acid reactive species (TBARS) in sera and aorta homogenates after administration of two doses of angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril and quinapril) in diet-induced hypercholesterolemia in rabbits. Sixty-four New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: i), equivalent to applied to humans, ii), dose 10 times higher. The animals were divided into 8 groups: control, standard fodder; B, special diet; C1, C2, special diet + captopril in doses 2.5 and 25 mg/kg/24 h, respectively; E1, E2, special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 h, respectively; Q1 and Q2, special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. In cholesterol-fed rabbits and in groups receiving lower doses of tested ACE inhibitors, the serum TBARS concentration at 6 months was significantly higher in comparison to the control. The higher doses of enalapril, quinapril and captopril, prevented the cholesterol-induced rise in TBARS concentration. Lower dose of captopril attenuated the rise in TBARS concentration, it was significantly lower in comparison to group B, but higher than in the control group. In animals from groups B, E1, C1, Q1 TBARS concentration in aortae was significantly higher as compared to control group. Both doses of captopril and higher doses of enalapril and quinapril inhibited the rise of lipid peroxides concentration induced by cholesterol-rich diet.

Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer.

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.

Serum total cholesterol and triglycerides levels in patients with lung cancer.

Epidemiological studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. The aim of our study was to evaluate serum levels of total cholesterol (TC) and triglycerides (TG) in patients with squamous cell and small cell lung cancer and their dependence on the histological type and the clinical stage of the neoplasm. Lung cancer patients (n=135) and healthy controls (n=39) entered the study. All lung cancer patients had higher rate of hypocholesterolemia and lower TC and TG levels than the control group. TC concentration was lower in lung cancer patients and in both histological types in comparison with the control group, TG level was lower only in patients with squamous cell lung cancer. There were no statistically significant differences of TC and TG levels between the histological types, or between the clinical stages of each histological type.