Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO multi-country survey of Maternal and Newborn Health.

OBJECTIVE: To evaluate the extent to which stillbirths affect international comparisons of preterm birth rates in low- and middle-income countries. DESIGN: Secondary analysis of a multi-country cross-sectional study. SETTING: 29 countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 258 215 singleton deliveries in 286 hospitals. METHODS: We describe how inclusion or exclusion of stillbirth affect rates of preterm births in 29 countries. MAIN OUTCOME MEASURES: Preterm delivery. RESULTS: In all countries, preterm birth rates were substantially lower when based on live births only, than when based on total births. However, the increase in preterm birth rates with inclusion of stillbirths was substantially higher in low Human Development Index (HDI) countries [median 18.2%, interquartile range (17.2-34.6%)] compared with medium (4.3%, 3.0-6.7%), and high-HDI countries (4.8%, 4.4-5.5%). CONCLUSION: Inclusion of stillbirths leads to higher estimates of preterm birth rate in all countries, with a disproportionately large effect in low-HDI countries. Preterm birth rates based on live births alone do not accurately reflect international disparities in perinatal health; thus improved registration and reporting of stillbirths are necessary. TWEETABLE ABSTRACT: Inclusion of stillbirths increases preterm birth rates estimates, especially in low-HDI countries.

Variations in very preterm birth rates in 30 high-income countries: are valid international comparisons possible using routine data?

OBJECTIVE: Concerns about differences in registration practices across countries have limited the use of routine data for international very preterm birth (VPT) rate comparisons. DESIGN: Population-based study. SETTING: Twenty-seven European countries, the United States, Canada and Japan in 2010. POPULATION: A total of 9 376 252 singleton births. METHOD: We requested aggregated gestational age data on live births, stillbirths and terminations of pregnancy (TOP) before 32 weeks of gestation, and information on registration practices for these births. We compared VPT rates and assessed the impact of births at 22-23 weeks of gestation, and different criteria for inclusion of stillbirths and TOP on country rates and rankings. MAIN OUTCOME MEASURES: Singleton very preterm birth rate, defined as singleton stillbirths and live births before 32 completed weeks of gestation per 1000 total births, excluding TOP if identifiable in the data source. RESULTS: Rates varied from 5.7 to 15.7 per 1000 total births and 4.0 to 11.9 per 1000 live births. Country registration practices were related to percentage of births at 22-23 weeks of gestation (between 1% and 23% of very preterm births) and stillbirths (between 6% and 40% of very preterm births). After excluding births at 22-23 weeks, rate variations remained high and with a few exceptions, country rankings were unchanged. CONCLUSIONS: International comparisons of very preterm birth rates using routine data should exclude births at 22-23 weeks of gestation and terminations of pregnancy. The persistent large rate variations after these exclusions warrant continued surveillance of VPT rates at 24 weeks and over in high-income countries. TWEETABLE ABSTRACT: International comparisons of VPT rates should exclude births at 22-23 weeks of gestation and terminations of pregnancy.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

Maternal and institutional characteristics associated with the administration of prophylactic antibiotics for caesarean section: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To illustrate the variability in the use of antibiotic prophylaxis for caesarean section, and its effect on the prevention of postoperative infections. DESIGN: Secondary analysis of a cross-sectional study. SETTING: Twenty-nine countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: Three hundred and fifty-nine health facilities with the capacity to perform caesarean section. METHODS: Descriptive analysis and effect estimates using multilevel logistic regression. MAIN OUTCOME MEASURES: Coverage of antibiotic prophylaxis for caesarean section. RESULTS: A total of 89 121 caesarean sections were performed in 332 of the 359 facilities included in the survey; 87% under prophylactic antibiotic coverage. Thirty five facilities provided 0-49% coverage and 77 facilities provided 50-89% coverage. Institutional coverage of prophylactic antibiotics varied greatly within most countries, and was related to guideline use and the practice of clinical audits, but not to the size, location of the institution or development index of the country. Mothers with complications, such as HIV infection, anaemia, or pre-eclampsia/eclampsia, were more likely to receive antibiotic prophylaxis. At the same time, mothers undergoing caesarean birth prior to labour and those with indication for scheduled deliveries were also more likely to receive antibiotic prophylaxis, despite their lower risk of infection, compared with mothers undergoing emergency caesarean section. CONCLUSIONS: Coverage of antibiotic prophylaxis for caesarean birth may be related to the perception of the importance of guidelines and clinical audits in the facility. There may also be a tendency to use antibiotics when caesarean section has been scheduled and antibiotic prophylaxis is already included in the routine clinical protocol. This study may act as a signal to re-evaluate institutional practices as a way to identify areas where improvement is possible.

Risk factors for spontaneous and provider-initiated preterm delivery in high and low Human Development Index countries: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To evaluate how the effect of maternal complications on preterm birth varies between spontaneous and provider-initiated births, as well as among different countries. DESIGN: Secondary analysis of a cross-sectional study. SETTING: Twenty-nine countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 299 878 singleton deliveries of live neonates or fresh stillbirths. METHODS: Countries were categorised into very high, high, medium and low developed countries using the Human Development Index (HDI) of 2012 by the World Bank. We described the prevalence and risk of maternal complications, their effect on outcomes and their variability by country development. MAIN OUTCOME MEASURES: Preterm birth, fresh stillbirth and early neonatal death. RESULTS: The proportion of provider-initiated births among preterm deliveries increased with development: 19% in low to 40% in very high HDI countries. Among preterm deliveries, the socially disadvantaged were less likely, and the medically high risk were more likely, to have a provider-initiated delivery. The effects of anaemia [adjusted odds ratio (AOR), 2.03; 95% confidence interval (CI), 1.84; 2.25], chronic hypertension (AOR, 2.28; 95% CI, 1.94; 2.68) and pre-eclampsia/eclampsia (AOR, 5.03; 95% CI, 4.72; 5.37) on preterm birth were similar among all four HDI subgroups. CONCLUSIONS: The provision of adequate obstetric care, including optimal timing for delivery in high-risk pregnancies, especially to the socially disadvantaged, could improve pregnancy outcomes. Avoiding preterm delivery in women when maternal complications, such as anaemia or hypertensive disorders, are present is important for countries at various stages of development, but may be more challenging to achieve.

Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization multicountry study.

OBJECTIVE: To investigate the risk of adverse pregnancy outcomes among adolescents in 29 countries. DESIGN: Secondary analysis using facility-based cross-sectional data of the World Health Organization Multicountry Survey on Maternal and Newborn Health. SETTING: Twenty-nine countries in Africa, Latin America, Asia and the Middle East. POPULATION: Women admitted for delivery in 359 health facilities during 2-4 months between 2010 and 2011. METHODS: Multilevel logistic regression models were used to estimate the association between young maternal age and adverse pregnancy outcomes. MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes among adolescent mothers. RESULTS: A total of 124 446 mothers aged ≤24 years and their infants were analysed. Compared with mothers aged 20-24 years, adolescent mothers aged 10-19 years had higher risks of eclampsia, puerperal endometritis, systemic infections, low birthweight, preterm delivery and severe neonatal conditions. The increased risk of intra-hospital early neonatal death among infants born to adolescent mothers was reduced and statistically insignificant after adjustment for gestational age and birthweight, in addition to maternal characteristics, mode of delivery and congenital malformation. The coverage of prophylactic uterotonics, prophylactic antibiotics for caesarean section and antenatal corticosteroids for preterm delivery at 26-34 weeks was significantly lower among adolescent mothers. CONCLUSIONS: Adolescent pregnancy was associated with higher risks of adverse pregnancy outcomes. Pregnancy prevention strategies and the improvement of healthcare interventions are crucial to reduce adverse pregnancy outcomes among adolescent women in low- and middle-income countries.

Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: We aimed to determine the prevalence and risks of late fetal deaths (LFDs) and early neonatal deaths (ENDs) in women with medical and obstetric complications. DESIGN: Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS). SETTING: A total of 359 participating facilities in 29 countries. POPULATION: A total of 308 392 singleton deliveries. METHODS: We reported on perinatal indicators and determined risks of perinatal death in the presence of severe maternal complications (haemorrhagic, infectious, and hypertensive disorders, and other medical conditions). MAIN OUTCOME MEASURES: Fresh and macerated LFDs (defined as stillbirths ≥ 1000 g and/or ≥28 weeks of gestation) and ENDs. RESULTS: The LFD rate was 17.7 per 1000 births; 64.8% were fresh stillbirths. The END rate was 8.4 per 1000 liveborns; 67.1% occurred by day 3 of life. Maternal complications were present in 22.9, 27.7, and 21.2% [corrected] of macerated LFDs, fresh LFDs, and ENDs, respectively. The risks of all three perinatal mortality outcomes were significantly increased with placental abruption, ruptured uterus, systemic infections/sepsis, pre-eclampsia, eclampsia, and severe anaemia. CONCLUSIONS: Preventing intrapartum-related perinatal deaths requires a comprehensive approach to quality intrapartum care, beyond the provision of caesarean section. Early identification and management of women with complications could improve maternal and perinatal outcomes.

Mode and timing of twin delivery and perinatal outcomes in low- and middle-income countries: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

OBJECTIVE: To describe the mode and timing of delivery of twin pregnancies at ≥34 weeks of gestation and their association with perinatal outcomes. DESIGN: Secondary analysis of a cross-sectional study. POPULATION: Twin deliveries at ≥34 weeks of gestation from 21 low- and middle-income countries participating in the WHO Multicountry Survey on Maternal and Newborn Health. METHODS: Descriptive analysis and effect estimates using multilevel logistic regression. MAIN OUTCOME MEASURES: Stillbirth, perinatal mortality, and neonatal near miss (use of selected life saving interventions at birth). RESULTS: The average length of gestation at delivery was 37.6 weeks. Of all twin deliveries, 16.8 and 17.6% were delivered by caesarean section before and after the onset of labour, respectively. Prelabour caesarean delivery was associated with older maternal age, higher institutional capacity and wealth of the country. Compared with spontaneous vaginal delivery, lower risks of neonatal near miss (adjusted odds ratio, aOR, 0.63; 95% confidence interval, 95% CI, 0.44-0.94) were found among prelabour caesarean deliveries. A lower risk of early neonatal mortality (aOR 0.12; 95% CI 0.02-0.56) was also observed among prelabour caesarean deliveries with nonvertex presentation of the first twin. The week of gestation with the lowest rate of prospective fetal death varied by fetal presentation: 37 weeks for vertex-vertex; 39 weeks for vertex-nonvertex; and 38 weeks for a nonvertex first twin. CONCLUSIONS: The prelabour caesarean delivery rate among twins varied largely between countries, probably as a result of overuse of caesarean delivery in wealthier countries and limited access to caesarean delivery in low-income countries. Prelabour delivery may be beneficial when the first twin is nonvertex. International guidelines for optimal twin delivery methods are needed.

Development of criteria for identifying neonatal near-miss cases: analysis of two WHO multicountry cross-sectional studies.

OBJECTIVE: To develop and test markers of neonatal severe morbidity for the identification of neonatal near-miss cases. DESIGN: This is a database analysis of two World Health Organization cross-sectional studies: the Global Survey on Maternal and Perinatal Health (WHOGS) and the Multicountry Survey on Maternal and Newborn Health (WHOMCS). SETTING: The WHOGS was performed in 373 health facilities in 24 countries (2004-2008). The WHOMCS was conducted in 359 health facilities in 29 countries (2010-2011). POPULATION: Data were collected from hospital records of all women admitted for delivery and their respective neonates. METHODS: Pragmatic markers (birthweight <1750 g, Apgar score at 5 minutes <7, and gestational age <33 weeks) were developed with WHOGS data and validated with WHOMCS data. The diagnostic accuracy of neonatal characteristics and management markers of severity was determined in the WHOMCS. RESULTS: This analysis included 290 610 liveborn neonates from WHOGS and 310 436 liveborn neonates from WHOMCS. The diagnostic accuracy of pragmatic and management markers of severity for identifying early neonatal deaths was very high: sensitivity, 92.8% (95% CI 91.8-93.7%); specificity, 92.7% (95% CI 92.6-92.8%); positive likelihood ratio, 12.7 (95% CI 12.5-12.9); negative likelihood ratio, 0.08 (95% CI 0.07-0.09); diagnostic odds ratio, 163.4 (95% CI 141.6-188.4). A positive association was found between the frequency of neonatal near-miss cases and Human Development Index. CONCLUSION: Newborn infants presenting selected markers of severity and surviving the first neonatal week could be considered as neonatal near-miss cases. This definition and criteria may be seen as a basis for future applications of the near-miss concept in neonatal health. These tools can be used to inform policy makers on how best to apply scarce resources for improving the quality of care and reducing neonatal mortality.

Synthesis and metabolism of arachidonyl- and eicosapentaenoyl-CoA in rat aorta.

In studies on the metabolism of polyunsaturated fatty acids, acyl-CoA synthetase for 5,8,11,14-20:4 (arachidonic acid) and 5,8,11,14,17-20:5 (eicosapentaenoic acid) and the incorporation of these fatty acids into complex lipids and their conversion to CO2 were investigated in rat aorta. The activity of acyl-CoA synthetase was 35.9 for arachidonic acid and 63.0 for eicosapentaenoic acid (nmol/mg protein per 10 min) and the apparent Km values were 45 microM for arachidonic acid and 56 microM for eicosapentaenoic acid. Inhibition of eicosapentaenoyl-CoA synthesis by arachidonic acid was stronger than that of arachidonyl-CoA synthesis by eicosapentaenoic acid. Arachidonic acid and eicosapentaenoic acid were mostly incorporated into phospholipids. The incorporation of these fatty acids into cholesterol ester and their conversion to CO2 were less than those of palmitic acid, but their incorporation into triacyglycerol was greater. The incorporation of these fatty acids into phosphatidylserine + phosphatidylinositol and phosphatidylethanolamine was also greater than that of palmitic acid. The patterns of incorporation of arachidonic acid and eicosapentaenoic acid were similar. The physiological roles of these polyunsaturated fatty acids and the interference of eicosapentaenoic acid in arachidonic acid metabolism are discussed on the basis of these results.

Fatty acid specificity of acyl-CoA synthetase in rat glomeruli.

The fatty acid specificity of acyl-CoA synthetase in rat glomeruli for physiologically and pathologically important long-chain fatty acids was studied. The apparent Michaelis constants (Km) for substrate fatty acids increased in the order, linolenic less than linoleic less than eicosapentaenoic less than arachidonic less than oleic less than palmitic acid. The maximum velocities with these fatty acids decreased in the order, oleic greater than linoleic greater than palmitic (approximately equal to) linolenic greater than arachidonic greater than eicosapentaenoic acid. The syntheses of radioactive arachidonyl-CoA and palmitoyl-CoA from radioactive arachidonic and palmitic acid, respectively, were both inhibited by all fatty acids mentioned above including the substrate fatty acids, their inhibitory effects being inversely correlated with their apparent Km values. These results suggest that the enzyme in glomeruli has a unique specificity for fatty acids and that there is no arachidonic acid-specific acyl-CoA synthetase in glomeruli. The possible contribution of the glomerular enzyme with this specificity to the abnormal fatty acid levels in diabetic animals is discussed.

Cytotoxic effects of paraquat and inhibition of them by vitamin E.

Paraquat causes failure of multiple organs including the liver in humans. The kinetics and mechanism of paraquat intoxication were studied using cultured rat hepatocytes. Paraquat induced time- and dose-dependent lactate dehydrogenase release, lipid peroxidation, and cell death, estimated as decrease in protein in cells attached to culture dishes. However, the increase in lipid peroxidation occurred after lactate dehydrogenase release had reached a plateau. Vitamin E inhibited the inductions of all these cytotoxic effects of paraquat. Kinetic studies showed that lipid peroxidation was a better indicator of cell death than lactate dehydrogenase release, because vitamin E inhibited the induction of cell death even when added 6 h after paraquat, when lactate dehydrogenase release had reached a plateau but lipid peroxidation had not. The present results strongly suggest that paraquat exerts its cytotoxicity by a mechanism involving oxidation reactions.

Hyaluronate synthesized by cultured skin fibroblasts derived from patients with Werner's syndrome.

Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate secreted into the medium by Werner's fibroblasts was 2-3-times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibroblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain length of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in the matrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain.

The receptor for advanced glycation end products mediates the chemotaxis of rabbit smooth muscle cells.

Long-term incubation of proteins with glucose leads to advanced glycation end products (AGEs) with fluorescence and a brown color. We recently demonstrated immunologically the intracellular AGE accumulation in smooth muscle cell (SMC)-derived foam cells in advanced atherosclerotic lesions. To understand the mechanism of AGE accumulation in these foam cells, we have now characterized the interaction of AGE proteins with rabbit-cultured arterial SMCs. In experiments at 4 degrees C, 125I-labeled AGE-bovine serum albumin (AGE-BSA) showed a dose-dependent saturable binding to SMCs with an apparent dissociation constant (Kd) of 4.0 microg/ml. In experiments at 37 degrees C, AGE-BSA underwent receptor-mediated endocytosis and subsequent lysosomal degradation. The endocytic uptake of 125I-AGE-BSA was effectively inhibited by unlabeled AGE proteins such as AGE-BSA and AGE-hemoglobin, but not by acetylated LDL and oxidized LDL, well-known ligands for the macrophage scavenger receptor (MSR). Moreover, the binding of 125I-AGE-BSA to SMCs was affected neither by amphoterin, a ligand for one type of the AGE receptor, named RAGE, nor by 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole-hexanoic acid-BSA, a ligand for the other AGE receptors, p60 and p90. This indicates that the endocytic uptake of AGE proteins by SMCs is mediated by an AGE receptor distinct from MSR, RAGE, p60, and p90. To examine the functional role of this AGE receptor, the migratory effects of AGE-BSA on these SMCs were tested. Incubation with 1-50 microg/ml of AGE-BSA for 14 h resulted in significant dose-dependent cell migration. The AGE-BSA-induced SMC migration was chemotactic in nature and was significantly inhibited (approximately 80%) by an antibody against transforming growth factor-beta (TGF-beta), and the amount of TGF-beta secreted into the culture medium from SMC by AGE-BSA was sevenfold higher than that of control, indicating that TGF-beta is involved in the AGE-induced SMC chemotaxis. These data suggest that AGE may play a role in SMC migration in advanced atherosclerotic lesions.

Secretion of a new growth factor, smooth muscle cell derived growth factor, distinct from platelet derived growth factor by cultured rabbit aortic smooth muscle cells.

In attempts to determine the mechanism of proliferation of arterial smooth muscle cells (SMC) in intimal atheromatous lesions, autocrine secretion of growth factors by SMC has recently received much attention. Here we report a new growth factor named smooth muscle cell derived growth factor (SDGF). Cultured rabbit medial SMC secreted SDGF for 1 week during their incubation in serum-free media only after at least 4 passages. SDGF differed from platelet derived growth factor (PDGF) physicochemically, immunologically, and biologically. The properties of SDGF also seemed different from those of other known growth factors that stimulate the proliferation of mesenchymal cells.

Age-related changes of long-chain fatty acid metabolism in rat liver.

Palmitate oxidation activity and the activities of several enzymes involved in long-chain fatty acid metabolism were examined in the liver of young adult (2-month-old) and senescent (32-month-old) female rats. Palmitate oxidation activity in rat liver mitochondria showed age-related decrease, as judged by the rates of both 14CO2 production and formation of radioactive acid-soluble products from [1-14C]palmitate. In addition, long-chain acyl-coenzyme A synthetase activity was found to be decreased in liver mitochondria and increased in liver microsomes in senescent rats. These results suggest that, in the rat liver, preferential channeling of long-chain fatty acids through the triacylglycerol synthetic pathway may increase with age, and as a result, energy production by their oxidation may decrease.

Fatty acid oxidation of rat brain microvessels in hypertension, aging and experimental diabetes.

Microvessels were prepared from rat brain and their fatty acid oxidation was investigated. This activity was much higher in brain microvessels than in other vessels or organs, suggesting that brain microvessels have a high capacity for energy production. The activity was decreased in some pathological conditions, such as hypertension, aging and diabetes mellitus. The relationship between changes in fatty acid oxidation activities and injuries of brain microvessels is discussed.

Lack of inhibition of DNA synthesis by prostaglandin I2 in cultured intimal smooth muscle cells from rabbits.

The negative control system for proliferation by prostaglandin I2 (PGI2) was studied in the smooth muscle cells (SMC) cultured from the thickened intima (intimal SMC) of rabbit aortas. Indomethacin was found to enhance DNA synthesis of medial SMC but not that of intimal SMC. Exogenously added PGI2 or its stable analogue, CS-570, was observed to inhibit DNA synthesis of medial SMC enhanced by indomethacin but not that of intimal SMC. These results indicate that medial SMC are negatively controlled by endogenous PGI2 and that intimal SMC have no such negative control system for cell proliferation. This lack of negative control may be one of the mechanisms underlying the rapid growth behavior of intimal SMC as compared to medial SMC.

Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC.

Migration of smooth muscle cells (SMC) in the arterial wall is important in the formation of intimal thickening. In this work, cultured SMC from the rat and rabbit aortic media at 2nd to 12th passages were found to secrete a potent migration factor for SMC which was named SMC-derived migration factor (SDMF). This factor stimulated the migration of SMC dose-dependently and its maximum activity was 2-8 times that of PDGF. Checker board analysis showed that SDMF was chemotactic, but not chemokinetic. In further studies, SDMF was found to be inactivated at 100 degrees C for 10 min or by trypsinization, but not inactivated by mercaptoethanol. This factor was not dialyzable. Molecular weight was approximately 500 kDa by a gel filtration. The activity was not inhibited by an anti-PDGF antibody or a fibronectin antiserum. These data suggest that SDMF is a potent migration factor for SMC and that SDMF is distinct from PDGF, fibronectin or other known migration factors. This autocrine system of secretion of SDMF by SMC and its induction of SMC migration may contribute to intimal thickening of the arterial wall in atherosclerosis.

Proliferation and LDL binding of cultured intimal smooth muscle cells from rabbits.

Cultured intimal smooth muscle cells (SMC) were prepared from rabbits in which a cannula had been inserted into the abdominal aorta 4 weeks previously. The patterns of growth proliferative rates, and lipoprotein metabolism of cultures of intimal and medial SMC from intact aortic media were compared. Intimal SMC proliferated more rapidly than medial SMC. Both low density lipoprotein (LDL) and acetylated LDL bound to intimal SMC, whereas only LDL bound to medial SMC. These findings suggest a phenotypic difference between intimal and medial SMC.