Biological aging is associated with an increased incidence of cerebrovascular disease. Recent fin... more Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.
In atherosclerosis, oxidative stress-induced vascular smooth muscle cells (SMCs) dysfunction is p... more In atherosclerosis, oxidative stress-induced vascular smooth muscle cells (SMCs) dysfunction is partially mediated by up-regulated NADPH oxidase (Nox); the mechanisms of enzyme regulation are not entirely defined. CCAAT/enhancer-binding proteins (C/EBP) regulate cellular proliferation and differentiation, and the expression of many inflammatory and immune genes. We aimed at elucidating the role of C/EBP in the regulation of Nox in SMCs exposed to pro-inflammatory conditions. Human aortic SMCs were treated with interferon-γ (IFN-γ) for up to 24 hrs. Lucigenin-enhanced chemiluminescence, real-time PCR, Western blot, promoter-luciferase reporter analysis and chromatin immunoprecipitation assays were employed to investigate Nox regulation. IFN-γ dose-dependently induced Nox activity and expression, nuclear translocation and up-regulation of C/EBPα, C/EBPβ and C/EBPδ protein expression levels. Silencing of C/EBPα, C/EBPβ or C/EBPδ reduced significantly but differentially the IFN-γ-induced up-regulation of Nox activity, gene and protein expression. In silico analysis indicated the existence of typical C/EBP sites within Nox1, Nox4 and Nox5 promoters. Transient overexpression of C/EBPα, C/EBPβ or C/EBPδ enhanced the luciferase level directed by the promoters of the Nox subtypes. Chromatin immunoprecipitation demonstrated the physical interaction of C/EBPα, C/EBPβ and C/EBPδ proteins with the Nox1/4/5 promoters. C/EBP transcription factors are important regulators of Nox enzymes in IFN-γ-exposed SMCs. Activation of C/EBP may induce excessive Nox-derived reactive oxygen species formation, further contributing to SMCs dysfunction and atherosclerotic plaque development. Pharmacological targeting of C/EBP-related signalling pathways may be used to counteract the adverse effects of oxidative stress.
Journal of submicroscopic cytology and pathology, 1994
Albumin is the major carrier of long chain free fatty acids, that are known to be heavily utilize... more Albumin is the major carrier of long chain free fatty acids, that are known to be heavily utilized by fat cells. To investigate the cellular structures involved in the interaction of albumin with preadipocytes, precursor fat cells isolated from rat epididymal fat pads were cultured in Dulbecco's modified Eagle's medium supplemented with 5% fetal calf serum and antibiotics. Cell differentiation was induced by 1.7 nM insulin added to the culture medium. The ensuing cells in various stages of differentiation were incubated with albumin, alone or bearing oleic acid, adsorbed to 5 nm gold particles (Alb-Au or Alb-OA-Au) for 10 min at 37 degrees C. As control, polyethyleneglycol-gold and IgG-gold complexes were used in same conditions. After extensive washing, the cell monolayer was fixed in 2.5% glutaraldehyde, and processed for electron microscopy. Examination of thin sections and morphometric analysis showed that: a) in the process of adipogenesis induced in vitro four cell typ...
The purpose of this study was to assess the expression of cell adhesion molecules ICAM-1 (interce... more The purpose of this study was to assess the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cell-derived foam cells. Hamster aortic endothelial cells (HAEC) in culture were exposed to hypercholesterolemic or normal homologous serum for 24 h. At the end of the incubation period, HAEC exposed to hypercholesterolemic serum exhibited numerous lipid droplets and had a general aspect of foam cells. When examined for the expression of ICAM-1 and VCAM-1 (by indirect immunofluorescence) normal HAEC expressed constitutively (to low level) on their surface these adhesion molecules; however HAEC-derived foam cells failed to display any labeling. To further assess these results, HAEC were first incubated with normal or hypercholesterolemic sera (as above) and then exposed to freshly isolated normal hamster blood monocytes. These experiments showed that monocytes adhered in small number to normal cells and failed to adhere to the surface of HAEC-derived foam cells. Together these data indicate that endothelial cell-derived foam cells: a) do not express ICAM-1 and VCAM-1 on their surface; b) have low or no adhesion properties for monocytes and c) may represent an appropriate experimental model to study the cellular alterations that take place in the advanced stages of atherosclerosis.
Journal of submicroscopic cytology and pathology, 1997
The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril maleate and captopril... more The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril maleate and captopril, on the progression of atherosclerosis was investigated. Golden Syrian hamsters were divided into five groups: controls (C), fed a standard chow diet; hypercholesterolemic animals (HH) induced by supplementing the diet with 3% cholesterol and 15% butter; HH treated with enalapril (20 mg/kg/day); HH treated with captopril (60 mg/kg/day) and HH treated simultaneously with enalapril and a calcium channel blocker, diltiazem (45 mg/kg/day). The drugs were administered for one month, concomitantly with the atherogenic diet. As compared to controls, in HH group a significant increase in serum cholesterol (approximately 5 fold) and ACE activity (approximately 3 fold) was found. In HH-treated animals, both drugs maintained the serum ACE activity within the normal values. However, the effect upon serum cholesterol was different: enalapril and its combination with diltiazem had a significant hypoc...
Journal of submicroscopic cytology and pathology, 1997
Arterial endothelial layer dysfunction is considered to be one of the most important events which... more Arterial endothelial layer dysfunction is considered to be one of the most important events which initiate the development of the atherosclerotic plaque and the cell cytoskeleton plays an essential role in maintaining the integrity of the endothelium exposed continuously to haemodynamic forces. The aim of this work was to study the modifications of the cytoskeletal proteins in the vascular endothelium exposed to atherogenic conditions. A hamster aortic endothelial cell line (HAEC) grown on glass coverslips was exposed for 24 h to hypercholesterolemic or normal homologous serum. Upon staining with Oil Red O and examination by phase contrast and fluorescence microscopy, HAEC incubated with hypercholesterolemic serum appeared heavily loaded with lipid droplets that showed a yellow autofluorescence in UV light and the general aspect of a foam cell. HAEC were incubated with: a) anti-actin serum; b) anti-vinculin monoclonal antibody (MoAb); c) anti-alpha actinin MoAb, and d) anti-talin Mo...
Journal of submicroscopic cytology and pathology, 1996
We compared the effect of two different calcium channel blockers (CCB), Nifedipine (1,4-dihydropy... more We compared the effect of two different calcium channel blockers (CCB), Nifedipine (1,4-dihydropyridine calcium antagonist) and Diltiazem (a benzothiazepine agent) on plasma components and the development of atherosclerotic plaque in experimental hypercholesterolemia. Golden male Syrian hamsters were divided into four groups: atherogenic animals (AT) induced by standard diet supplemented with 3% cholesterol and 15% butter; AT animals treated with Nifedipine (20 or 60 mg/kg/day); AT hamsters treated with Diltiazem (45 mg/kg/day) and controls (C), fed a standard chow diet. For one month, the drugs were administered concomitantly with the atherogenic diet. During the experiment, serum cholesterol, free calcium and angiotensin-converting enzyme (ACE) activity values were determined. Specimens from the lesion-prone areas: aortic valves, coronary arteries, and aortic arch, were collected and processed for light and electron microscopy. The results show that the atherogenic diet induces a ...
Journal of submicroscopic cytology and pathology, 1991
The presence of albumin binding sites on the abluminal front of vascular endothelium was examined... more The presence of albumin binding sites on the abluminal front of vascular endothelium was examined on the capillaries of the adipose tissue. The experimental procedure consisted in injecting interstitially within the rat epididymal fat and epicardial fat, albumin (alone or bearing oleic acid) either conjugated with gold particles (Alb-Au or Alb-OA-Au) or radioiodinated [( 125I]-Alb). In controls, polyethyleneglycol-gold complex (PEG-Au) and [125I]-IgG were used as tracers. The results revealed that: a) albumin binding sites are expressed on the abluminal front of endothelium especially concentrated on plasmalemmal vesicles; b) the retrotranscytosis of albumin conjugates from the interstitium to the capillary lumen is a poorly represented process; c) the binding of the tracers used appears to be time and concentration dependent; d) albumin conjugates do not bind significantly to plasmalemmal vesicles of adipocytes, pericytes and smooth muscle cells; e) PEG-Au and [125I]-IgG do not sho...
High glucose induces vascular smooth muscle cell (SMC) dysfunction by generating oxidative stress... more High glucose induces vascular smooth muscle cell (SMC) dysfunction by generating oxidative stress attributable, in part, to the up-regulated NADPH oxidases (Nox). We have attempted to elucidate the high-glucose-generated molecular signals that mediate this effect and hypothesize that products of high-glucose-induced lipid peroxidation regulate Nox by activating peroxisome proliferator-activated receptors (PPARs). Human aortic SMCs were exposed to glucose (5.5-25 mM) or 4-hydroxynonenal (1-25 μM, 4-HNE). Lucigenin assay, real-time polymerase chain reaction, western blot, and promoter analyses were employed to investigate Nox. We found that high glucose generated an increase in Nox activity and expression. It also promoted oxidative stress that consequently induced lipid peroxidation, which resulted in the production of 4-HNE. Pharmacological inhibition of Nox activity significantly reduced the formation of high-glucose-induced 4-HNE. Exposure of SMCs to non-cytotoxic concentrations (...
Biological aging is associated with an increased incidence of cerebrovascular disease. Recent fin... more Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.
Biological aging is associated with an increased incidence of cerebrovascular disease. Recent fin... more Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.
In atherosclerosis, oxidative stress-induced vascular smooth muscle cells (SMCs) dysfunction is p... more In atherosclerosis, oxidative stress-induced vascular smooth muscle cells (SMCs) dysfunction is partially mediated by up-regulated NADPH oxidase (Nox); the mechanisms of enzyme regulation are not entirely defined. CCAAT/enhancer-binding proteins (C/EBP) regulate cellular proliferation and differentiation, and the expression of many inflammatory and immune genes. We aimed at elucidating the role of C/EBP in the regulation of Nox in SMCs exposed to pro-inflammatory conditions. Human aortic SMCs were treated with interferon-γ (IFN-γ) for up to 24 hrs. Lucigenin-enhanced chemiluminescence, real-time PCR, Western blot, promoter-luciferase reporter analysis and chromatin immunoprecipitation assays were employed to investigate Nox regulation. IFN-γ dose-dependently induced Nox activity and expression, nuclear translocation and up-regulation of C/EBPα, C/EBPβ and C/EBPδ protein expression levels. Silencing of C/EBPα, C/EBPβ or C/EBPδ reduced significantly but differentially the IFN-γ-induced up-regulation of Nox activity, gene and protein expression. In silico analysis indicated the existence of typical C/EBP sites within Nox1, Nox4 and Nox5 promoters. Transient overexpression of C/EBPα, C/EBPβ or C/EBPδ enhanced the luciferase level directed by the promoters of the Nox subtypes. Chromatin immunoprecipitation demonstrated the physical interaction of C/EBPα, C/EBPβ and C/EBPδ proteins with the Nox1/4/5 promoters. C/EBP transcription factors are important regulators of Nox enzymes in IFN-γ-exposed SMCs. Activation of C/EBP may induce excessive Nox-derived reactive oxygen species formation, further contributing to SMCs dysfunction and atherosclerotic plaque development. Pharmacological targeting of C/EBP-related signalling pathways may be used to counteract the adverse effects of oxidative stress.
Journal of submicroscopic cytology and pathology, 1994
Albumin is the major carrier of long chain free fatty acids, that are known to be heavily utilize... more Albumin is the major carrier of long chain free fatty acids, that are known to be heavily utilized by fat cells. To investigate the cellular structures involved in the interaction of albumin with preadipocytes, precursor fat cells isolated from rat epididymal fat pads were cultured in Dulbecco's modified Eagle's medium supplemented with 5% fetal calf serum and antibiotics. Cell differentiation was induced by 1.7 nM insulin added to the culture medium. The ensuing cells in various stages of differentiation were incubated with albumin, alone or bearing oleic acid, adsorbed to 5 nm gold particles (Alb-Au or Alb-OA-Au) for 10 min at 37 degrees C. As control, polyethyleneglycol-gold and IgG-gold complexes were used in same conditions. After extensive washing, the cell monolayer was fixed in 2.5% glutaraldehyde, and processed for electron microscopy. Examination of thin sections and morphometric analysis showed that: a) in the process of adipogenesis induced in vitro four cell typ...
The purpose of this study was to assess the expression of cell adhesion molecules ICAM-1 (interce... more The purpose of this study was to assess the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cell-derived foam cells. Hamster aortic endothelial cells (HAEC) in culture were exposed to hypercholesterolemic or normal homologous serum for 24 h. At the end of the incubation period, HAEC exposed to hypercholesterolemic serum exhibited numerous lipid droplets and had a general aspect of foam cells. When examined for the expression of ICAM-1 and VCAM-1 (by indirect immunofluorescence) normal HAEC expressed constitutively (to low level) on their surface these adhesion molecules; however HAEC-derived foam cells failed to display any labeling. To further assess these results, HAEC were first incubated with normal or hypercholesterolemic sera (as above) and then exposed to freshly isolated normal hamster blood monocytes. These experiments showed that monocytes adhered in small number to normal cells and failed to adhere to the surface of HAEC-derived foam cells. Together these data indicate that endothelial cell-derived foam cells: a) do not express ICAM-1 and VCAM-1 on their surface; b) have low or no adhesion properties for monocytes and c) may represent an appropriate experimental model to study the cellular alterations that take place in the advanced stages of atherosclerosis.
Journal of submicroscopic cytology and pathology, 1997
The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril maleate and captopril... more The effect of two angiotensin converting enzyme (ACE) inhibitors, enalapril maleate and captopril, on the progression of atherosclerosis was investigated. Golden Syrian hamsters were divided into five groups: controls (C), fed a standard chow diet; hypercholesterolemic animals (HH) induced by supplementing the diet with 3% cholesterol and 15% butter; HH treated with enalapril (20 mg/kg/day); HH treated with captopril (60 mg/kg/day) and HH treated simultaneously with enalapril and a calcium channel blocker, diltiazem (45 mg/kg/day). The drugs were administered for one month, concomitantly with the atherogenic diet. As compared to controls, in HH group a significant increase in serum cholesterol (approximately 5 fold) and ACE activity (approximately 3 fold) was found. In HH-treated animals, both drugs maintained the serum ACE activity within the normal values. However, the effect upon serum cholesterol was different: enalapril and its combination with diltiazem had a significant hypoc...
Journal of submicroscopic cytology and pathology, 1997
Arterial endothelial layer dysfunction is considered to be one of the most important events which... more Arterial endothelial layer dysfunction is considered to be one of the most important events which initiate the development of the atherosclerotic plaque and the cell cytoskeleton plays an essential role in maintaining the integrity of the endothelium exposed continuously to haemodynamic forces. The aim of this work was to study the modifications of the cytoskeletal proteins in the vascular endothelium exposed to atherogenic conditions. A hamster aortic endothelial cell line (HAEC) grown on glass coverslips was exposed for 24 h to hypercholesterolemic or normal homologous serum. Upon staining with Oil Red O and examination by phase contrast and fluorescence microscopy, HAEC incubated with hypercholesterolemic serum appeared heavily loaded with lipid droplets that showed a yellow autofluorescence in UV light and the general aspect of a foam cell. HAEC were incubated with: a) anti-actin serum; b) anti-vinculin monoclonal antibody (MoAb); c) anti-alpha actinin MoAb, and d) anti-talin Mo...
Journal of submicroscopic cytology and pathology, 1996
We compared the effect of two different calcium channel blockers (CCB), Nifedipine (1,4-dihydropy... more We compared the effect of two different calcium channel blockers (CCB), Nifedipine (1,4-dihydropyridine calcium antagonist) and Diltiazem (a benzothiazepine agent) on plasma components and the development of atherosclerotic plaque in experimental hypercholesterolemia. Golden male Syrian hamsters were divided into four groups: atherogenic animals (AT) induced by standard diet supplemented with 3% cholesterol and 15% butter; AT animals treated with Nifedipine (20 or 60 mg/kg/day); AT hamsters treated with Diltiazem (45 mg/kg/day) and controls (C), fed a standard chow diet. For one month, the drugs were administered concomitantly with the atherogenic diet. During the experiment, serum cholesterol, free calcium and angiotensin-converting enzyme (ACE) activity values were determined. Specimens from the lesion-prone areas: aortic valves, coronary arteries, and aortic arch, were collected and processed for light and electron microscopy. The results show that the atherogenic diet induces a ...
Journal of submicroscopic cytology and pathology, 1991
The presence of albumin binding sites on the abluminal front of vascular endothelium was examined... more The presence of albumin binding sites on the abluminal front of vascular endothelium was examined on the capillaries of the adipose tissue. The experimental procedure consisted in injecting interstitially within the rat epididymal fat and epicardial fat, albumin (alone or bearing oleic acid) either conjugated with gold particles (Alb-Au or Alb-OA-Au) or radioiodinated [( 125I]-Alb). In controls, polyethyleneglycol-gold complex (PEG-Au) and [125I]-IgG were used as tracers. The results revealed that: a) albumin binding sites are expressed on the abluminal front of endothelium especially concentrated on plasmalemmal vesicles; b) the retrotranscytosis of albumin conjugates from the interstitium to the capillary lumen is a poorly represented process; c) the binding of the tracers used appears to be time and concentration dependent; d) albumin conjugates do not bind significantly to plasmalemmal vesicles of adipocytes, pericytes and smooth muscle cells; e) PEG-Au and [125I]-IgG do not sho...
High glucose induces vascular smooth muscle cell (SMC) dysfunction by generating oxidative stress... more High glucose induces vascular smooth muscle cell (SMC) dysfunction by generating oxidative stress attributable, in part, to the up-regulated NADPH oxidases (Nox). We have attempted to elucidate the high-glucose-generated molecular signals that mediate this effect and hypothesize that products of high-glucose-induced lipid peroxidation regulate Nox by activating peroxisome proliferator-activated receptors (PPARs). Human aortic SMCs were exposed to glucose (5.5-25 mM) or 4-hydroxynonenal (1-25 μM, 4-HNE). Lucigenin assay, real-time polymerase chain reaction, western blot, and promoter analyses were employed to investigate Nox. We found that high glucose generated an increase in Nox activity and expression. It also promoted oxidative stress that consequently induced lipid peroxidation, which resulted in the production of 4-HNE. Pharmacological inhibition of Nox activity significantly reduced the formation of high-glucose-induced 4-HNE. Exposure of SMCs to non-cytotoxic concentrations (...
Biological aging is associated with an increased incidence of cerebrovascular disease. Recent fin... more Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.
Uploads
Papers by Monica Raicu