摘要:

The process of intimal thickening after de-endothelializing injury to the rat carotid artery is dependent on the migration of smooth muscle cells from the media. Recent reports have suggested that platelet-derived growth factor may be an important mediator of migration after injury. We have addressed this issue by directly determining smooth muscle cell migration in injured arteries of animals depleted of platelets and after administration of an antibody that blocks platelet-derived growth factor. Because there is a reported association between plasminogen activator synthesis and smooth muscle cell migration, we assayed the activity levels of plasminogen activators after arterial injury and also assessed the effect of a plasmin inhibitor on migration. The data suggest that platelet-derived growth factor, released by platelets at sites of arterial injury, is an endogenous mediator of smooth muscle cell migration; that plasmin generation, catalyzed by tissue-type plasminogen activator, is necessary for migration; and that one way in which platelet-derived growth factor may act is by stimulation of the synthesis of tissue-type plasminogen activator by smooth muscle cells.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Previous investigations have shown that abnormalities in the postheparin plasma levels of the lipolytic enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are correlated with variations in plasma high-density lipoprotein cholesterol (HDL-C) levels. The present study was performed to determine correlations between the postheparin plasma activities of these two enzymes and HDL levels in a sizable number of subjects with low HDL-C levels. Two types of low-HDL subjects were investigated: 159 male subjects with low HDL-C (<40 mg/dL) and normal triglyceride (<250 mg/dL) levels (the low-HDL group) and 80 male subjects with low HDL-C (<40 mg/dL) and elevated triglyceride (>250 mg/dL) levels (the low-HDL/high-TG group). Postheparin plasma activities of LPL and HTGL were determined in these two groups, and these levels were compared with those obtained from 51 normolipidemic (normal-HDL) male subjects. Postheparin LPL activities were significantly lower in the low-HDL and low-HDL/high-TG groups (mean±SD, 9.9±2.9 and 10.4+3.0 mmol/h per liter, respectively;p<.001 for both) compared with the normal-HDL group (12.5±3.7 mmol/h per liter). Conversely, postheparin HTGL activities were significantly higher in the low-HDL and low-HDL/high-TG groups (39.3+16.2 and 44.4+16.7 mmol/h per liter, respectively;p<.001 for both) compared with the normal-HDL group (29.7±11.3 mmol/h per liter). Consequently, mean LPL/HTGL ratios were markedly lower in the two low-HDL groups compared with the normal-HDL group. Within each group, analysis revealed no specific relationships between the enzyme activities and potential modifying factors (cigarette smoking and β-adrenergic blocking agents). When subjects from each group who were neither smokers nor taking $-blockers were compared, HTGL activities, but not LPL activities, were significantly different for the low-HDL groups compared with the normal-HDL group. The results of this study suggest that high HTGL activity and low LPL activity are both important contributors to low HDL levels in both normotriglyceridemic and hypertriglyceridemic subjects. However, in the absence of potential modifying factors, high HTGL activity appears to be the major change in lipolytic enzymes associated with HDL levels.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Mobile receptors on surfaceand suspension-activated platelets bind a variety of specific and nonspecific antigens and particulates and clear them from the plasma membrane to channels of the open canalicular system (OCS). The present study examined the interaction of platelets with latex spherules of increasing size to identify the role of mobile receptors and binding sites in hemostatic physiology. Small latex spherules 0.09 to 3.13 /tm in average diameter were cleared from peripheral margins to central zones and the OCS on surface-activated platelets and from the surface membrane to the OCS of platelets in suspension. Larger spheres, 6.4 /tm in diameter, could not be moved across the membranes of solid phaseand fluid phase-activated platelets. Instead, platelets moved their surface membranes through the contact sites fixed on the surface of immobile spheres, bringing interior membranes of the OCS channels to the latex. This change, in which mobile membranes move through fixed contact sites rather than mobile receptor complexes moving across plasma membranes, results in evagination of almost all OCS channels on large latex spherules. A similar mechanism may be involved in the interaction of platelets with relatively flat surfaces, such as denuded subendothelium.

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Acute ischemic heart disease is associated with alterations in the cardiac adenylate cyclase system response, although the specificity and mechanism of these events are unknown. We studied the characteristics of inhibitory (G,) and stimulatory (Gs) GTP-binding regulatory proteins (G proteins) of adenylate cyclase in erythrocyte membranes of patients (n=16) with nonacute ischemic heart disease resulting from coronary atherosclerosis. Gswas measured by reconstitution with the resolved catalytic unit of adenylate cyclase and by cholera toxin-catalyzed ADP-ribosylation of a 42 -kD protein; G, was tested as a 41-kD substrate of pertussis toxin-catalyzed ADP-ribosylation. G s activity was decreased by 27 ±2% in the cholate extract and by 25±3% in the supernatant of guanosine 5′-(y-thio)triphosphate-treated membranes. The amount of cholera toxin substrate was decreased by 33 ±3%, and the pertussis toxin substrate was increased by 27±5% compared with healthy subjects (n=10). All changes in G-protein characteristics appear to be specific relative to other erythrocyte membrane proteins and hemoglobin. Those patients who have a decreased Gs possess approximately normal G, and those with increased G, showed no change in Gs. Patients with increased G, (normal Gs) exhibited more severe deterioration of their coronary arteries than did patients with decreased G s (normal Gj) (p<.05), but these two groups did not differ significantly in serum lipids, hormones, drug therapy, historical data, or baseline assessment (i><0.05).

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1049-8834    

出版商:OVID    

年代:1993

数据来源: OVID