elastin and Cerebrovascular-Disorders

Many processes involved in the pathogenesis of atherosclerosis result in modifications of the extracellular matrix. These changes not only determine the mechanical stability of atherosclerotic lesions but can directly or indirectly influence further development of the lesions. The purpose of the present study was to compare the matrix composition of human carotid plaques from symptomatic patients with those obtained from patients without symptoms. Furthermore, matrix changes related to age were studied.. Thirty atherosclerotic carotid plaques were removed by endarterectomy from 27 patients and divided into 2 groups on the basis of the presence of ipsilateral symptoms. The plaques were homogenized, and the total levels of the major components of the extracellular matrix were determined.. Plaques associated with symptoms were characterized by increased levels of elastin (1.58+/-0.46 versus 1.24+/-0.40 mg/g wet wt; P=0.03) and decreased levels of hydroxyapatite (45.1+/-46.3 versus 131.4+/-111.7 mg/g wet wt; P=0.02) compared with asymptomatic plaques. The increase in elastin in plaques from symptomatic patients was due to elevated levels of an intermediate-size fraction, as determined by liquid chromatography. Collagen and sulfated glycosaminoglycans were present in equal amounts in both groups. Elastin content in carotid plaques decreased with age.. Carotid plaques from symptomatic patients have lower levels of hydroxyapatite than those from asymptomatic patients. The present study also raises the possibility that non-cross-linked forms of elastin, increased in plaques associated with symptoms, could be a marker of plaque vulnerability and/or directly induce harmful cellular activities or increase lipoprotein retention in the vascular wall.

Topics: Age Factors; Aged; Aging; Biomarkers; Carotid Artery Diseases; Cerebrovascular Disorders; Collagen; Durapatite; Elastin; Endarterectomy, Carotid; Extracellular Matrix; Female; Glycosaminoglycans; Humans; Male; Risk Factors

1. Vessel wall fragments consisting of collagen, elastin and other insoluble proteins were prepared from the aortas of 6 month old WKY and SHRSP and dead, elderly humans. 2. Prolonged incubations of these fragments with pepsin below or at 30 degrees C resulted in different amounts of insoluble materials containing similar or larger proportions of collagen and other insoluble proteins than the respective vessel fragments. The amounts of the pepsin-insoluble materials obtained from SHRSP were larger than those from WKY but were much smaller than those from elderly humans. 3. The elastins isolated from the vessel fragments were solubilized by pepsin much more effectively than the respective vessel fragments. 4. The pepsin-insoluble materials from WKY were composed of thin mesh-shaped materials, while these materials from both rats did not contain a significant number of distinctive fibrils of collagen, the materials from elderly humans did contain numerous distinctive fibrils of collagen. 5. Large fractions of both the collagen and other proteins in the pepsin-insoluble materials were solubilized by incubation with a crude bacterial collagenase below 30 degrees C or by incubation with pepsin above 40 degrees C where the triple-helical regions of the collagens were unfolded. 6. These results appear to indicate that the aortic wall of SHRSP contains larger amounts of some insoluble components that immobilize the collagen fibrils than that of WKY, but the aortic walls of elderly humans contain much larger amounts of these components than that of SHRSP.

Topics: Aged; Animals; Aorta; Cerebrovascular Disorders; Collagen; Elastin; Humans; Hypertension; Middle Aged; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR; Rats, Inbred WKY

A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.

Topics: Alzheimer Disease; Brain; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Disorders; Elastin; Humans; Immunohistochemistry; Italy; Male; Microscopy, Electron; Middle Aged; Neurofibrillary Tangles; Pedigree; Spinal Cord; Tomography, X-Ray Computed

This study examined effects of local reductions in mean and pulse pressures on cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). WKY and SHRSP underwent clipping of one carotid artery at 1 month of age. At 10-12 months of age, mechanics of pial arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies were performed to expose pial arterioles in the sham and clipped cerebral hemispheres. Stress-strain relations were calculated from measurements of pial arteriolar pressure (servo null), diameter, and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantitate individual components in the arteriolar wall. Before deactivation of smooth muscle with EDTA, mean (Pm) and pulse (Pp) pressures were significantly less (p less than 0.05) in clipped than in sham arterioles in WKY (Pm, 63 +/- 2 versus 73 +/- 2 mm Hg; Pp, 23 +/- 3 versus 30 +/- 3 mm Hg) and SHRSP (Pm, 94 +/- 4 versus 110 +/- 4 mm Hg; Pp, 27 +/- 2 versus 38 +/- 3 mm Hg). Cross-sectional area of the arteriolar wall was less (p less than 0.05) in clipped than in sham arterioles in both groups of rats (1,403 +/- 125 versus 1,683 +/- 125 microns2 in WKY; 1,436 +/- 72 versus 1,926 +/- 134 microns2 in SHRSP). There was a correlation between cross-sectional area of the vessel wall and pulse pressure (r2 = 0.66), but not mean pressure (r2 = 0.09). During maximal dilatation with EDTA, the stress-strain curve was shifted to the left in clipped arterioles of SHRSP, but not of WKY, which indicates that carotid clipping in SHRSP reduces passive distensibility of cerebral arterioles. The proportion of distensible components in the vessel wall (smooth muscle, elastin, and endothelium) was reduced in clipped arterioles in SHRSP, but not in WKY. These findings suggest that 1) vascular hypertrophy of cerebral arterioles is related more closely to pulse pressure than to mean pressure, and 2) reduction of pial arteriolar pressure completely prevents cerebral vascular hypertrophy and attenuates increases in passive distensibility of cerebral arterioles in SHRSP.

Topics: Animals; Arterioles; Blood Pressure; Cerebrovascular Circulation; Cerebrovascular Disorders; Collagen; Disease Susceptibility; Elastin; Hypertrophy; Muscle, Smooth; Pia Mater; Rats; Rats, Inbred SHR; Rats, Inbred WKY

The degradation of elastin during various pathological processes such as emphysema or arteriosclerosis was demonstrated by several investigators. In the present work, we adapted an ELISA technique for the determination of elastin peptide (EP) levels in human sera and plasma, in healthy and arteriosclerotic subjects. This test makes use of human aorta elastin hydrolyzed by a chemical procedure (kappa-elastin) instead of EP produced by pancreatic or leukocyte elastase. Polyclonal antibodies to this antigen were obtained in rabbits. The indirect ELISA procedure is sensitive, specific and reproducible. No correlation could be demonstrated between EP level and anti-EP antibody concentration of IgG or IgM types determined in the same serum samples. These antibodies did not interfere with EP determinations. EP concentration did not change with age in control subjects. In obliterative arteriosclerosis of the legs and in type IIb hyperlipoproteinemia, EP levels showed a marked increase, while in hypertension, ischemic heart disease and diabetes mellitus, the increase was moderate. In stroke, only slight changes were observed. In type IV hyperlipoproteinemia, EP levels were lower than in controls.

Topics: Adult; Age Factors; Aged; Aorta; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Hydrolysis; Hyperlipoproteinemias; Hypertension; Immunoglobulin G; Immunoglobulin M; Leg; Middle Aged; Peptides; Sensitivity and Specificity

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.

Topics: Adult; Aged; Antibodies; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Male; Middle Aged; Peptides

Topics: Animals; Aorta; Cerebrovascular Disorders; Elastin; Muscle, Smooth, Vascular; Pancreatic Elastase; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY

Topics: Adult; Aged; Autoantibodies; Carotid Artery Diseases; Cerebral Infarction; Cerebrovascular Disorders; Complement System Proteins; Elastin; Giant Cell Arteritis; Humans; Immune Complex Diseases; Immunoglobulins; Male; Middle Aged; Temporal Arteries

Topics: Animals; Aorta; Cerebrovascular Disorders; Collagen; Elastin; Hypertension; Rats; Rats, Inbred Strains

Topics: Animals; Aorta, Thoracic; Cerebrovascular Disorders; Elastin; Hypertension; Muscle, Smooth, Vascular; Rats

Topics: Aging; Amino Acids; Animals; Aorta; Cerebrovascular Disorders; Diet; Elastin; Female; Hypertension; Male; Rats

Topics: Adolescent; Adult; Age Factors; Aged; Aorta; Arteries; Arteriosclerosis; Black People; Calcium; Cerebral Arteries; Cerebrovascular Disorders; Child; Child, Preschool; Cholesterol; Collagen; Coronary Disease; Coronary Vessels; Elastin; Female; Hexosamines; Histocytochemistry; Humans; Infant; Infant, Newborn; Lipids; Male; Middle Aged; Phospholipids; Sex Factors; South Africa; Thrombosis; Triglycerides; White People