Biomedical subjects

Vaiva Lesauskaite

Publications and source records attributed to Vaiva Lesauskaite.

9 recordsLinked to original sources

PubMed2006

Expression of matrix metalloproteinases, their tissue inhibitors, and osteopontin in the wall of thoracic and abdominal aortas with dilatative pathology.

Matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of aortic aneurysms. We studied 2 groups of patients: 15 with dilatative pathology of the ascending thoracic aorta and 17 with aneurysm of the abdominal aortic wall (AAA). We compared the expression of MMPs, tissue inhibitors of matrix metalloproteinases (TIMPs), and osteopontin in the wall of thoracic and abdominal aneurysms. In AAA, MMP-9 and TIMP-1 expression in inflammatory cells was higher than in smooth muscle cells (SMCs) (median score: 3.5 versus 1, P < .0001; 2 versus 1, P < .04, respectively), whereas MMP-2 demonstrated higher expression in SMCs than in inflammatory cells (median score: 0 versus 4, P < .0001). In ATA, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3, and osteopontin expression in SMCs was higher than in inflammatory cells (median score: 3 versus 0, P < .0001; 4 versus 1, P < .0005; 2 versus 0, P < .001; 5 versus 2, P < .0001; 2 versus 0, P < .005; and 5 versus 1.5, P < .0001, respectively), when both inflammatory cells of the media and the adventitia were considered together. The cellular expression of MMP-9 and their tissue inhibitors TIMP-1, TIMP-2, and TIMP-3 differs in the dilatative pathology of abdominal and thoracic aortas, so the hypothetical model of morphogenesis of AAA cannot completely explain the formation of dilatative pathology of the ascending thoracic aorta.

Adult↗

PubMed2005

Effects of cadmium ions on the initial stage of translation and the cell death in mouse liver.

OBJECTIVE: To evaluate in vivo and in vitro effects of cadmium ions on the activities of mice liver tRNA(Leu)and leucyl-tRNA synthetase and on the type of liver cells death. MATERIAL AND METHODS: White laboratory mice were intoxicated by intraperitoneal injection of cadmium chloride solution (1.6 mg cadmium ions/1 kg of body weigh). Total tRNAs were isolated by adding ethanol and isopropanol into the phenol-deproteinized supernatant of mouse liver homogenate. Post-mitochondrial fraction of the liver cells was used as a source of leucyl-tRNA synthetase. Acceptor activity of tRNA(Leu)and activity of leucyl-tRNA synthetase were measured in tRNA aminoacylation reaction with [14C]-labeled leucine as a substrate. An apoptotic cell death was assessed by the TUNEL assay using in situ cell death detection kit. DNA degradation was verified by electrophoresis. RESULTS: It was determined that 2-24 hours after intoxication with sublethal dose of cadmium ions the acceptor activity of mice liver tRNA(Leu)was decreased by 43-73% as compared to control. At the same time intervals, the activity of leucyl-tRNA synthetase was reduced about 20-30%. Experiments in vitro revealed that 10-20 microM concentrations of cadmium ions suppressed the activities of mice liver tRNA(Leu)and leucyl-tRNA synthetase by 40-98%. No significant difference was observed between the number of TUNEL positive apoptotic liver cells in the control mice and 24 hours after intoxication with cadmium chloride. Electrophoresis revealed extensive degradation of nuclear DNA. CONCLUSIONS: Cadmium ions significantly reduce activities of tRNA(Leu)and leucyl-tRNA synthetase in vivo and in vitro. There is no significant difference between the number of apoptotic cells in the control liver specimens and in those after 24 hours of intoxication with cadmium chloride. In latter specimens DNA electrophoresis revealed as extensive degradation of DNA, which is characteristic to the cell necrosis.

Animals↗

PubMed2005

Effects of cadmium and zinc ions on mitotic activity and protein synthesis in mouse liver.

OBJECTIVE: To evaluate the in vivo effects of cadmium and zinc ions on mitotic activity and protein synthesis in mouse liver. MATERIAL AND METHODS: White outbred mice were injected intraperitoneally with cadmium chloride solution (14 micromoles cadmium per 1 kg of body mass) and/or with zinc sulfate solution (48 micromoles zinc per 1 kg of body mass). Histological slides were examined by light microscopy. For each specimen, the number of mitotic cells was counted in 10 randomly selected reference areas. Protein synthesis was evaluated by incorporation of [14C]-labeled leucine into newly synthesized peptides and proteins. RESULTS: We found that the mitotic index of mouse liver cells was increased for periods of 2-8 h after cadmium chloride injection; after 24 h the mitotic index significantly diminished. These data indicate a possible increase in liver cell regeneration during the initial 8 h following acute cadmium exposure. Zinc ions did not affect liver mitotic activity, and, interestingly, decreased the mitotic index in the liver of cadmium-treated mice to control levels. An examination of the kinetics of protein synthesis in mouse liver over a 24 h period after cadmium chloride injection revealed that incorporation diminished by 38% at 2 h, then increased 51% by 8 h and again decreased by 32% at 24 h as compared to control. Zinc ions increased protein synthesis in mouse liver 8 h after zinc sulfate injection. In assessing the effects of cadmium and zinc ions in vivo, it appeared that zinc ions tended to protect protein synthesis in response to cadmium ions but only at 2 h after cadmium intoxication. CONCLUSIONS: Zinc ions are capable of normalizing an increase in the mitotic index of liver cells at the early stage of cadmium poisoning (up to 8 h) and to protect the liver translation machinery against inhibition by cadmium.

Animals↗

PubMed2004

Apoptosis of cardiomyocytes in explanted and transplanted hearts. Comparison of results from in situ TUNEL, ISEL, and ISOL reactions.

We assessed the efficiency of detecting myocyte apoptosis within human hearts using in situ enzymatic reactions in paraffin-embedded tissue samples: in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), and in situ oligoligation (ISOL). The reactions were carried out in explanted hearts (idiopathic dilatative cardiomyopathy, n = 6; ischemic heart disease, n = 3) and in endomyocardial biopsy specimens (EMBs; n = 32) obtained from transplanted human hearts. The results were verified by DNA laddering. The ISOL reaction led to a significantly (P = .027) smaller number of false-positive results (2/41 [5%]) compared with assessment by ISEL (9/41 [22%]) or TUNEL (9/41 [22%]). Only 1 ISEL+ apoptotic cardiomyocyte was found in specimens from explanted hearts. Among the EMBs, 1 specimens had TUNEL+ apoptotic cardiomyocytes and 1 specimen had ISEL+ apoptotic cardiomyocytes. This implies that verifying results by independent methods must be used for TUNEL and ISEL techniques. A smaller number of false-positive results makes interpretation of ISOL results easier, although the sensitivity of this reaction remains to be established.

Apoptosis↗

PubMed2004

[Pathobiological determinants of atherosclerosis in youths: data from a macromorphometric and histomorphometric investigation of the aorta and coronary arteries].

We present a review of data from epidemiological and morphological studies carried out in Kaunas of atherosclerosis in youths. Since 1985, Kaunas has been a Collaborating Center involved with the World Health Organization and International Society and Federation of Cardiology studying the pathobiological determinants of atherosclerosis in youth. During the pilot study (1985-1987), we estimated the prevalence and extent of atherosclerotic lesions in the aorta and coronary arteries correlated to various risk factors in Kaunas residents aged 5 to 44 years. Within the framework of this international study, we compared histomorphometric characteristics of arteries collected from trauma victims aged 5 to 34 years in Budapest (Hungary), Heidelberg (Germany), Kaunas (Lithuania), Yaounde (Cameroon), and Mexico City (Mexico). These data revealed that males from countries with a high mortality from ischemic heart disease (Hungary, Lithuania, Germany) tended to have thicker intima in the thoracic and abdominal aorta and left anterior descending coronary artery than did males from countries with low mortality from ischemic heart disease (Mexico, Cameroon). We detected an increased mean intimal thickness of the abdominal aorta in male smokers aged 25-34 years. Males with hypertension aged 15-24 and 25-34 years had a thicker intima in the aorta and left anterior descending coronary artery than normotensive males. The morphological and epidemiological studies of atherosclerosis in youths carried out in Kaunas demonstrated that aortic and coronary atherosclerotic lesions appeared as early as childhood and advanced until the lesions become clinically apparent in adulthood. Histomorphometric findings support the postulate that increased intimal thickness can be considered a structural determinant of atherogenesis. These data draw attention to the means for the primary prevention of atherosclerosis in youth.

Adolescent↗

PubMed2004

[Results of morphologic epidemiologic study of coronary arteries in Kaunas population aged 20-69 years: atherosclerotic lesions and their interrelationship].

OBJECTIVE: The object of study was the type, frequency and extent, as well as correlation of atherosclerotic lesions in Kaunas population aged 20-69 years. RESULTS: The frequency and intimal area of raised atherosclerotic lesions (fibrous and complicated plaque and calcinosis) are age-dependent. The increase of raised lesions area seems to alter at different decades of life. In men the most substantial progression in left anterior descending artery was observed at the fourth-fifth, in right coronary artery--at the fifth, and in both arteries of women - at the sixth decade of life. The area of fatty streaks is not dependent on age and comprises approximately 4-5% of intimal surface. We observed weak negative correlation between area of raised lesions and fatty streaks, and strong correlation between the area of all type of raised lesions in all three coronary arteries. CONCLUSIONS: The coronary artery atherosclerosis is progressing with age. Age decades, when increase of raised lesion area is observed, correspond to age periods, in which mortality due to ischemic heart disease increases significantly.

Adult↗

PubMed2003

[Programmed cellular death and atherogenesis: from molecular mechanisms to clinical aspects].

Numerous recent investigations on the development and morphology of atherosclerotic lesions have shown programmed cell death or apoptosis to be an important factor in atherogenesis. Enzymes known as caspases are essential for completion of the apoptotic program. With regard to the origin of signals inducing apoptosis, there are two ways of initiating caspase activation: (a) cellular death receptor-mediated activation; and (b) activation mediated by mitochondrial permeability and expression of the p53 oncogene. Both of these pathways are involved in atherogenesis. Oxidative stress, angiotensin II and cholesterol overload are the primary factors that induce apoptosis in vascular cells. Considering apoptosis in endothelial cells, exposed phosphatidylserine on the cell membrane activates thrombin increasing the probability of arterial thromboses. Further progression of atherosclerosis is promoted by the formation of apoptotic bodies with oxidized phospholipids exposed on the membrane; these also activate adhesion of monocytes. Apoptosis of smooth muscle cells is usually observed in the fibrous portion of an atherosclerotic plaque in which the cells produce collagen important for plaque stability. As apoptosis occurs in smooth muscle cells, the fibrous cap grows thinner. This can result in both plaque rupture, formation of thrombi as well as calcification of the plaque from apoptotic smooth muscle cells remnants. Smooth muscle cells apoptosis is beneficial in that it offers protection to the walls of arteries against proliferative restenosis induced by invasive procedures. Apoptosis of macrophages contributes to the formation and progression of the lipidic core and promotes thrombosis of atherosclerosis in damaged arteries. By contrast, apoptosis of macrophages diminishes the production of matrix methaloproteinases that decompose collagen fibers. New facts concerning the effects of antioxidants (selenium, vitamin C and vitamin E), inhibitors of angiotensin converting enzyme, beta-blockers, calcium chanel blockers, and statins are also considered in this review.

Adrenergic beta-Antagonists↗

PubMed2002

[Morphogenesis of thoracic aorta aneurysms: investigation of matrix metalloproteinases and their tissue inhibitors].

The matrix metalloproteinases are a large group of proteases with a central role of the degradation of all types of extracellular matrix. The present study investigated expression of matrix metalloproteinases (MMP-1, -2, -9) and their inhibitors (TIMP-1, -2) in chronic Aneurysm of the Thoracic Aorta (ATA) and Post-Stenotic Dilatation of the ascending aorta due to valvular aortic stenosis (PSD). Fragments of the ascending aorta that had been taken from the patients during coronary by-pass surgery were used as controls. Immunohistochemical investigation showed that medical SMC in the samples taken from aortas with ATA and PDS expressed a stronger immunoreactivity for MMP-1, -2, -9 and TIMP-1, -2 as compared to controls. It can be suggested that during formation of ATA and PSD, production of MMPs and TIMPS by medial smooth muscle cells is of great importance.

Age Factors↗

PubMed2002

[Programmed cell death: molecular mechanisms and detection].

Apoptosis or programmed cell death is genetically determined process to destroy cells for the maintaining of cellular homeostasis in the tissue. This paper reviews the current knowledge on the molecular mechanisms of apoptosis. Activation of cysteine proteases called caspases plays a major role in the execution of apoptosis. These activated caspases selectively cleave cellular proteins, which result in apoptotic morphology (internucleosomal fragmentation of DNA into 180-200 base pair pieces, shrinkage of the cell and the nucleus as well and fragmentation of the cell into apoptotic bodies) and death of the cell. Now two pathways of caspase activation are reported. The first through triggering of cellular death-receptor superfamily. The second is mitochondrial pathway induced by the changes of the expression of pro- and anti-apoptotic genes in the cell. It leads to release of cytochrome c and apoptosis inducing factor from mitochondria. The paper reviews also currently used methods of detection of apoptotic cells in tissue samples, causes of false-positive or false-negative results of ISEL and TUNEL in situ reactions.

Aortic Aneurysm, Thoracic↗