Big data from small animals: integrating multi-level environmental data into the Dog Aging Project.

Environmental exposures can have large impacts on health outcomes. While many resources have been dedicated to understanding how humans are influenced by the environment, few efforts have been made to study the role of built and natural environmental features on animal health. The Dog Aging Project (DAP) is a longitudinal community science study of aging in companion dogs. Using a combination of owner-reported surveys and secondary sources linked through geocoded coordinates, DAP has captured home, yard and neighbourhood variables for over 40,000 dogs. The DAP environmental data set spans four domains: the physical and built environment; chemical environment and exposures; diet and exercise; and social environment and interactions. By combining biometric data, measures of cognitive function and behaviour, and medical records, DAP is attempting to use a big-data approach to transform the understanding of how the surrounding world affects the health of companion dogs. In this paper, the authors describe the data infrastructure developed to integrate and analyse multi-level environmental data that can be used to improve the understanding of canine co-morbidity and aging.

L'impact des expositions environnementales sur la santé est parfois considérable. Si diverses ressources ont été consacrées à décrire l'influence de l'environnement sur les humains, les efforts visant à étudier l'effet des paramètres environnementaux, tant naturels qu'anthropiques, sur la santé animale sont plus rares. Le Dog Aging Project (DAP) est une étude scientifique longitudinale à base communautaire portant sur le vieillissement du chien de compagnie. À partir d'observations notifiées par les propriétaires de chiens et de sources secondaires reliées par des coordonnées de géocodage, le DAP a réuni des variables sur le foyer d'habitation, l'environnement extérieur immédiat et le voisinage de plus de 40 000 chiens. Les séries de données environnementales du DAP couvrent quatre domaines : l'environnement physique et bâti ; l'environnement chimique et les expositions ; le régime alimentaire et la dépense physique ; et les interactions et l'environnement social. En combinant les données biométriques, les mesures du fonctionnement cognitif et comportemental et les dossiers médicaux, le DAP cherche à utiliser l'approche des mégadonnées pour transformer notre perception de la manière dont le monde qui nous entoure affecte la santé des chiens de compagnie. Les auteurs décrivent l'infrastructure des données mise au point pour intégrer et analyser des données environnementales multi-niveaux, afin de mieux comprendre les phénomènes de comorbidité et de vieillissement chez le chien.

La exposición a factores ambientales puede tener muchas e importantes repercusiones en los resultados sanitarios. Si bien se han dedicado cuantiosos recursos a aprehender la influencia del entorno en las personas, poco se ha hecho para estudiar el modo en que las características del medio, tanto natural como artificial, repercuten en la salud de los animales. El proyecto sobre Envejecimiento canino [Dog Aging Project: DAP] es un estudio longitudinal de ciencia ciudadana centrado en el envejecimiento de los perros de compañía. Combinando la información de encuestas realizadas a propietarios y de fuentes secundarias y vinculando los datos a coordenadas geográficas codificadas, el DAP ha permitido reunir información de variables ligadas al hogar, el jardín y el barrio de más de 40 000 perros. El conjunto de datos ambientales del DAP cubre cuatro grandes ámbitos: medio físico y urbanizado; condiciones químicas del entorno y exposición a sustancias químicas; régimen alimentario y ejercicio; y medio e interacciones sociales. Pasando por el uso combinado de datos biométricos, historias clínicas y mediciones de la función cognitiva y el comportamiento, el DAP apunta ahora a emplear técnicas de trabajo con macrodatos para hacer evolucionar nuestras ideas sobre la influencia del mundo que nos rodea en la salud de los perros de compañía. Los autores describen la infraestructura de datos establecida para integrar y analizar datos ambientales multiestratificados que nos ayuden a conocer mejor los procesos de comorbilidad y envejecimiento en el perro.

Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

BACKGROUND: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. METHODS: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. RESULTS: The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. CONCLUSIONS: MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells.

Apoptosis of smooth muscle cells is a common feature of vascular lesions but its pathophysiological significance is not known. We demonstrate that signals initiated by regulated Fas-associated death domain protein overexpression in rat vascular smooth muscle cells in the carotid artery induce expression of monocyte-chemoattractant protein-1 and interleukin-8, and cause massive immigration of macrophages in vivo. These chemokines, and a specific set of other pro-inflammatory genes, are also upregulated in human vascular smooth muscle cells during Fas-induced apoptosis, in part through a process that requires interleukin-1alpha activation. Induction of a pro-inflammatory program by apoptotic vascular smooth muscle cells may thus contribute to the pathogenesis of vascular disease.

Cytochalasin B inhibition of endothelial proliferation at wound edges in vitro.

Cytochalasin B prevents both migration and wound-associated replication when applied to wounded monolayers of bovine endothelium in tissue culture. The normal low background rate of replication in undisturbed areas of the cultures is not inhibited by cytochalasin B. These results suggest that some form of movement may be required for initiation of wound-associated replication by endothelial cells.

Identification of a Ca2(+)-dependent cell-cell adhesion molecule in endothelial cells.

Confluent cultures of aortic endothelial cells contain two different cell-cell adhesion mechanisms distinguished by their requirement for calcium during trypsinization and adhesion. A hybridoma clone was isolated producing a monoclonal antibody Ec6C10, which inhibits Ca2(+)-dependent adhesion of endothelial cells. There was no inhibition of Ca2(+)-independent adhesion of endothelial cells and only a minor effect on Ca2(+)-dependent adhesion of smooth muscle cells. Immunoblotting analysis shows that the antibody Ec6C10 recognizes a protein in endothelial but not epithelial cells with an apparent molecular weight of 135,000 in reducing conditions and 130,000 in non-reducing conditions. Monoclonal antibody Ec6C10 reacts with an antigen at the cell surface as shown by indirect immunofluorescence of confluent endothelial cells in a junctional pattern outlining the cobblestone morphology of the monolayer. Removal of extracellular calcium increased the susceptibility of the antigen recognized by antibody Ec6C10 to proteolysis by trypsin. The role of the Ca2(+)-dependent cell adhesion molecule in organization of the dense peripheral microfilament band in confluent endothelial cells was examined by adjusting the level of extracellular calcium to modulate cell-cell contact. Addition of the monoclonal antibody Ec6C10 at the time of the calcium switch inhibited the extent of formation of the peripheral F-actin band. These results suggest an association between cell-cell contact and the peripheral F-actin band potentially through the Ca2(+)-dependent CAM.

The role of membrane-membrane interactions in the regulation of endothelial cell growth.

A cell surface preparation from confluent endothelial cells can inhibit DNA synthesis of actively growing endothelial cells. The decrease in the rate of [3H]thymidine incorporation is concentration dependent and levels off at 47% of the control. The preparation has no affect on the growth of vascular smooth muscle cells. A similar preparation from smooth muscle cells does not show inhibitory activity with either endothelial or smooth muscle cells. The inhibition of growth can also be demonstrated by a decrease in thymidine index and growth rate. The inhibition is transient and after 48 h, the growth rate is similar to that of the control. In a wound edge assay, both migration and proliferation are inhibited. The inhibitory activity is partially labile to trypsin and abolished by pepsin, heating at 100 degrees C, or reduction. Cell surface iodination and analysis of the proteins removed by urea treatment by SDS polyacrylamide gel electrophoresis show at least 11 bands with apparent molecular weights from 250,000 to 18,000. These radiolabeled proteins, as well as the active component of the cell surface preparation, are sedimentable at 100,000 g for 1 h. They are both solubilized in 30 mM octyl glucoside but not by treatment with 0.1 M sodium carbonate, pH 11.5. These results suggest that the activity is due to a cell-surface membrane fraction and may provide a basis for studying the mechanism of density-dependent inhibition of growth in a normal cell of defined origin.

An endothelial cell-derived growth factor.

Cell-free plasma-derived serum (PDS) is deficient in the platelet-derived growth factor and will not support the growth of 3T3 cells, fibroblasts, or smooth muscle cells. However, when PDS-containing medium is preincubated with endothelial cells, the medium becomes modified so that it will support growth. The activity produced by the endothelial cells results from a polypeptide of 10,000 to 30,000 daltons which has several features that differ from those of the platelet-derived growth factor, including heat instability and lack of adsorption to CM Sephadex.

The platelet glycoprotein IIb/IIIa-like protein in human endothelial cells promotes adhesion but not initial attachment to extracellular matrix.

On platelets the membrane glycoprotein IIb/IIIa complex (GPIIb/IIIa) functions in adhesive interactions with fibrinogen, von Willebrand factor, and fibronectin. However, the function of GPIIb/IIIa-like proteins on endothelial cells, as well as the ligand(s) the complex binds, is unknown. Using a highly specific polyclonal antibody we have explored the function of GPIIb/IIIa-like proteins on human umbilical vein endothelial cells (HUVE). Analysis by immunoblotting shows that this antiserum recognizes the endothelial GPIIIa-like protein of the complex. The IgG fraction of the polyclonal antiserum and its Fab' fragments detach confluent and subconfluent HUVE from extracellular substrata. The effect of the anti-GPIIb/IIIa IgG is not toxic as the detached cells maintain their viability after trypsinization and replating. Anti-GPIIb/IIIa IgG does not inhibit HUVE binding to extracellular matrix or purified fibronectin in an attachment assay despite the presence of intact GPIIb/IIIa on HUVE detached from substrate by various methods. Apparently, the GPIIb/IIIa-like protein on HUVE is important in normal HUVE adhesion to the extracellular matrix, but it is not required in the initial attachment of HUVE to extracellular matrix.

PDGF ligand and receptor gene expression during repair of arterial injury.

Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha-receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.

Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets.

Damage to the vessel wall is a signal for endothelial migration and replication and for platelet release at the site of injury. Addition of transforming growth factor-beta (TGF-beta) purified from platelets to growing aortic endothelial cells inhibited [3H]thymidine incorporation in a concentration-dependent manner. A transient inhibition of DNA synthesis was also observed in response to wounding; cell migration and replication are inhibited during the first 24 hours after wounding. By 48 hours after wounding both TGF-beta-treated and -untreated cultures showed similar responses. Flow microfluorimetric analysis of cell cycle distribution indicated that after 24 hours of exposure to TGF-beta the cells were blocked from entering S phase, and the fraction of cells in G1 was increased. The inhibition of the initiation of regeneration by TGF-beta could allow time for recruitment of smooth muscle cells into the site of injury by other platelet components.

Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.

CXCL12 provides a chemotactic signal-directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR = 0.74, 95% CI: 0.56-0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5'-flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56-0.93; recessive model OR = 0.35, 95% CI: 0.12-0.97; and log-additive model OR = 0.72, 95% CI: 0.57-0.90). A stepwise procedure identified rs17885289, rs266085 and 3'-untranslated region (UTR) SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3'-UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.

Cholesteryl ester transfer protein (CETP) genetic variation and early onset of non-fatal myocardial infarction.

Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early-onset non-fatal MI risk in a population-based case-control study from western Washington State. Genotyping for the CETP -2708 G/A, -971 A/G, -629 A/C, Intron-I TaqI G/A and exon-14 A/G (I405V) SNPs was performed in 578 cases with first acute non-fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In-person interviews and non-fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age- and race-adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (-2708 G, -971 G, -629 C, TaqI G and exon-14 A), the fully-adjusted multiplicative model identified haplotype G (-2708 G, -971 A, -629 A, TaqI G and exon-14 G) was associated with a 4.0-6.0-fold increased risk of MI for each additional copy; [95%CI 2.4-14.8] and haplotype B (-2708 G, -971 G, -629 A, TaqI A and exon-14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 - 0.75]. An evolutionary-based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early-onset non-fatal MI. This association was found to be independent of HDL-C levels. These data and the sex-specific findings require confirmation in other populations.

Micro magnetic resonance angiography of the finger in systemic sclerosis.

OBJECTIVE: To characterize vascular lesions in SSc disease with high-resolution magnetic resonance angiography (Micro-MRA) of the finger. METHODS: Eight SSc subjects and eight age- and sex-matched healthy controls were recruited for this study. Among the SSc subjects, the mean +/- s.d. age was 54.5 +/- 4.9 yrs, and the mean +/- s.d. duration of disease was 8.3 +/- 8.4 yrs. The numbers of SSc subjects that had telangiectasia, calcinosis and impaired finger flexion were 3, 2 and 3, respectively. The 2D time-of-flight micro-MRA was performed on a 3T clinical MRI scanner using a custom-designed finger coil with an in-plane resolution of 0.16 x 0.21 mm(2) and slice thickness of 1.2 mm. The data for the proper palmar digital artery lumen area, the number of visible dorsal digital veins and a semi-quantitative vascular score, which evaluates the overall integrity of digital vessels, were independently evaluated by two experienced reviewers who were blinded to the status of the subject. RESULTS: Micro-MRA detected significant differences in the digital vasculature between SSc subjects and healthy volunteers. The SSc subjects had a significantly decreased digital artery lumen area (0.13 +/- 0.06 vs 0.53 +/- 0.26 mm(2), P < 0.001), a reduced number of digital veins (0.63 +/- 1.06 vs 3.13 +/- 0.99, P = 0.001) and a lowered overall vascular score (1.75 +/- 1.04 vs 3.5 +/- 0.53, P = 0.001). The study also found that both the digital artery lumen area (Pearson's; r = -0.72, P = 0.044) and vascular scores (Spearman's; rho = -0.75, P = 0.047) of the SSc subjects were inversely correlated with the duration of the disease. CONCLUSIONS: Micro-MRA can be used to identify and quantitatively characterize the vascular disease in SSc fingers. The parameters derived from micro-MRA could potentially be used as prospective biomarkers for clinical evaluation.

Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques.

We studied death of human vascular smooth muscle cells derived from coronary plaques and normal coronary arteries and aorta. Cells from normal arteries underwent death only upon removal of serum growth factors. In contrast, plaque-derived cells died even in high serum conditions, and death increased after serum withdrawal. Death was characteristically by apoptosis in both normal and plaque-derived cells, as determined by time-lapse videomicroscopy, electron microscopy, and DNA fragmentation patterns. IGF-1 and PDGF were identified as potent survival factors in serum, whereas EGF and basic fibroblast growth factor had little effect. Stable expression of bcl-2, a protooncogene that regulates apoptosis in other cell lines, protected smooth muscle cells from apoptosis, although there was no detectable difference in endogenous bcl-2 expression between cells from plaques or normal vessels. We conclude that apoptosis of human vascular smooth muscle cells is regulated by both specific gene products and local cytokines acting as survival factors. Apoptosis may therefore regulate cell mass in the normal arterial wall and the higher rates of apoptosis seen in plaque smooth muscle cells may ultimately contribute to plaque rupture and breakdown and thus to the clinical sequelae of atherosclerosis.

Skeletal myoblast transplantation for repair of myocardial necrosis.

Myocardial infarcts heal by scarring because myocardium cannot regenerate. To determine if skeletal myoblasts could establish new contractile tissue, hearts of adult inbred rats were injured by freeze-thaw, and 3-4.5 x 10(6) neonatal skeletal muscle cells were transplanted immediately thereafter. At 1 d the graft cells were proliferating and did not express myosin heavy chain (MHC). By 3 d, multinucleated myotubes were present which expressed both embryonic and fast fiber MHCs. At 2 wk, electron microscopy demonstrated possible satellite stem cells. By 7 wk the grafts began expressing beta-MHC, a hallmark of the slow fiber phenotype; coexpression of embryonic, fast, and beta-MHC continued through 3 mo. Transplanting myoblasts 1 wk after injury yielded comparable results, except that grafts expressed beta-MHC sooner (by 2 wk). Grafts never expressed cardiac-specific MHC-alpha. Wounds containing 2-wk-old myoblast grafts contracted when stimulated ex vivo, and high frequency stimulation induced tetanus. Furthermore, the grafts could perform a cardiac-like duty cycle, alternating tetanus and relaxation, for at least 6 min. Thus, skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically. Because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.

Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function.

Production of transforming growth factor beta 1 during repair of arterial injury.

Repair of arterial injury produced by balloon angioplasty leads to the formation of a neointima and a narrowing of the vascular lumen. In this study, we examined the possibility that smooth muscle cells (SMC) in injured rat carotid arteries are stimulated to produce type-1 transforming growth factor-beta (TGF-beta 1) during neointima formation in vivo. Levels of TGF-beta 1 transcripts (2.4 kb) were significantly increased within 6 h after carotid injury and reached a maximum (five to sevenfold) by 24 h. Regenerating left carotids had sustained increases in TGF-beta 1 mRNA levels (about fivefold) over the next 2 wk, during which time a substantial neointimal thickening was formed. No changes in basal TGF-beta 1 mRNA levels were found in contralateral uninjured carotids at any of the times examined. Immunohistochemical studies showed that a large majority of neointimal SMC were stained for TGF-beta 1 protein in an intracellular pattern, consistent with active TGF-beta 1 synthesis in this tissue. Neointima formation and TGF-beta 1 immunoreactivity were correlated with increases in fibronectin, collagen alpha 2(I), and collagen alpha 1(III) gene expression. Infusion of purified, recombinant TGF-beta 1 into rats with a preexisting neointima produced a significant stimulation of carotid neointimal SMC DNA synthesis. These results suggest that TGF-beta 1 plays an important role as an endogenous growth regulatory factor produced by neointimal SMC themselves during progressive neointimal thickening after balloon angioplasty.

Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization.

Platelet-derived growth factor (PDGF) mRNA, and mRNA for its receptor, have been localized to specific cell types within the human atherosclerotic plaque, using in situ hybridization. The predominant cell types found to express PDGF A and B chain mRNA are mesenchymal-appearing intimal cells and endothelial cells, respectively, with little or no expression detected in macrophages. The distribution of PDGF receptor mRNA containing cells was also examined and found to be localized predominantly in the plaque intima.

Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques.

In an earlier report, we used differential cloning to identify genes that might be critical in controlling arterial neointima formation (Giachelli, C., N. Bae, D. Lombardi, M. Majesky, and S. Schwartz. 1991. Biochem. Biophys. Res. Commun. 177:867-873). In this study, we sequenced the complete cDNA and conclusively identified one of these genes, 2B7, as rat osteopontin. Using immunochemistry and in situ hybridization, we found that medial smooth muscle cells (SMC) in uninjured arteries contained very low levels of osteopontin protein and mRNA. Injury to either the adult rat aorta or carotid artery using a balloon catheter initiated a qualitatively similar time-dependent increase in both osteopontin protein and mRNA in arterial SMC. Expression was transient and highly localized to neointimal SMC during the proliferative and migratory phases of arterial injury, suggesting a possible role for osteopontin in these processes. In vitro, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), and angiotensin II (AII), all proteins implicated in the rat arterial injury response, elevated osteopontin expression in confluent vascular SMC. Finally, we found that osteopontin was a novel component of the human atherosclerotic plaque found most strikingly associated with calcified deposits. These data implicate osteopontin as a potentially important mediator of arterial neointima formation as well as dystrophic calcification that often accompanies this process.

Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty.

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (SMC) in vitro, but its activities in vivo remain largely undefined. We infused recombinant PDGF-BB (0.01-0.30 mg/kg per d i.v.) into rats subjected to carotid injury. PDGF-BB produced a small increase (two- to threefold) in medial SMC proliferation. More importantly, PDGF-BB greatly increased (20-fold) the intimal thickening and the migration of SMC from the media to the intima during the first 7 d after injury. These data provide support for the hypothesis that PDGF, and perhaps other platelet factors, might play an important role in the movement of mesenchymal cells into zones of injury undergoing repair.