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Biomedical subjects

M Rabinovitch

Publications and source records attributed to M Rabinovitch.

At least 91 records · Page 5Linked to original sources
PubMed1994

The endogenous vascular elastase that governs development and progression of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme related to the serine proteinase adipsin.

We showed previously a cause and effect relationship between increased activity of an endogenous vascular elastase (EVE) and experimentally induced pulmonary hypertension in rats. We now report the isolation and characterization of EVE. Degenerate oligonucleotides synthesized to homologous sequences in serine elastases were used in a PCR with rat pulmonary artery (PA) cDNA. The PCR product hybridized to a 1.2-kb mRNA and the intensity of hybridization was threefold increased in RNA from rat hypertensive PA at a timepoint when EVE activity was increased. The PCR product was used to screen a cDNA library and sequences obtained encoded rat adipsin. We then used immunoaffinity to purify EVE. An antibody to the elastin-binding protein was used to remove this competitor of elastase from the PA extract and the elastolytic activity increased 100-fold. The enzyme was purified using an antibody that recognizes NH2-terminal sequences of serine proteinases and the eluate was further purified using an antibody raised against recombinant adipsin. A single band at 20 kD immunoreactive with the adipsin antibody was resolved as an active enzyme on an elastin substrate gel. Immunogold labeling with an antibody to an adipsin peptide sequence localized EVE to PA smooth muscle cells. This is the first isolation of EVE; it appears to be a novel enzyme related to the serine proteinase adipsin originally found in adipose tissue.

Amino Acid Sequence↗
PubMed1994

Alpha 1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity.

We investigated whether alpha 1-antitrypsin (alpha 1-AT) might protect neonatal rats from the pulmonary parenchymal and vascular effects resulting from hyperoxic exposure. Neonatal rats born into and maintained in hyperoxia (60% fraction of inspired oxygen) or room air were injected with a loading dose of alpha 1-AT (72 mg/kg) followed by 36 mg/kg every 72 h or with vehicle during the first 14 d of life. At the end of the experimental period, we measured body weight, lung compliance, lung volume, alveoli per mm2, and total number of alveoli and assessed right ventricular hypertrophy and vascular changes consisting of medial hypertrophy, muscular extension into peripheral, normally nonmuscular arteries, and number of peripheral arteries relative to alveoli. Our data show that alpha 1-AT treatment prevented the reduced lung compliance observed in the untreated hyperoxia-exposed neonatal rats, as well as the right ventricular hypertrophy and the associated vascular changes of medial hypertrophy of muscular arteries and muscularization of distal arteries. Reduced lung compliance in the hyperoxic but alpha 1-AT-untreated rats was associated with a reduction in lung elastin compared with room-air or alpha 1-AT-treated rats. In room-air rats, alpha 1-AT treatment increased lung compliance but also reduced the number of arteries relative to the number of alveoli, a feature that was not, however, associated with right ventricular hypertrophy. Our data suggest that supplemental alpha 1-AT might restore the imbalance in elastolytic activity induced by hyperoxia and thereby alleviate the toxic effects on lung parenchymal and vascular development.

Animals↗
PubMed1994

Fusion between large phagocytic vesicles: targeting of yeast and other particulates to phagolysosomes that shelter the bacterium Coxiella burnetii or the protozoan Leishmania amazonensis in Chinese hamster ovary cells.

This report examines the fusion of phagocytic vesicles with the large phagolysosome-like vacuoles induced in Chinese hamster ovary cells by the bacterium Coxiella burnetti or the Protozoan flagellate Leishmania amazonensis. Infection by these organisms is compatible with cell survival and multiplication. Fusion was inferred from the transfer of microscopically identifiable particles from donor to target vesicles. Donor vesicles contained heat-killed yeast, zymosan, beta-glucan or latex beads taken up by the host cells. Yeast and zymosan were also coated with Concanavalin A to increase their uptake by the cells (Goldman, R., Exp. Cell Res. 104, 325-334, 1977). Particle localization, routinely ascertained by phase-contrast microscopy, was confirmed by confocal laser fluorescence and by transmission electron microscopy. Coxiella vacuoles admitted all the particles tested and transfer took place whether the particles were given to the cells prior to or after infection. Transfer of uncoated or Concanavalin-A-coated yeast or zymosan was dependent on the number of particles ingested and on the incubation period (between 2 and 24 hours). Furthermore, the transfer step was quite efficient, since over 85% of the particles ingested entered Coxiella vacuoles at all particle to cell ratios examined. The fraction of uncoated or Concanavalin-A-coated yeast or zymosan transferred to Leishmania vacuoles was consistently lower and diminished at higher particle loads. In addition, only rarely did latex beads enter these vacuoles. The models proposed may be useful for the delineation of biochemical and molecular mechanisms involved in the fusion of large phagocytic vesicles and the modulation of the latter by cellular and pathogen-derived signals.

Animals↗
PubMed1994

Gas bubble emboli detected by transcranial Doppler sonography in patients with prosthetic heart valves: a preliminary report.

After observing spikes in the Doppler signal of cerebral arteries of patients with neurologic symptoms and prosthetic heart valves, we then studied two groups of patients with prosthetic heart valves: seven patients with neurologic symptoms and 65 asymptomatic patients. Using transcranial Doppler sonography of the middle cerebral artery, we found Doppler spikes in six symptomatic and 24 asymptomatic patients with mechanical heart valves. No spikes were found in one symptomatic and 21 asymptomatic patients with biological valves or in 20 asymptomatic patients with mechanical valves. We concluded that gas cavitation during the opening or closure of the valve, producing bubble emboli, is the most probable explanation for these Doppler spikes in patients with mechanical prosthetic heart valves.

Aged↗
PubMed1994

Post-cardiac transplant arteriopathy in piglets is associated with fragmentation of elastin and increased activity of a serine elastase.

In experimental piglets after heterotopic heart transplant, we observed an immune/inflammatory response in the coronary arteries with increased expression of interleukin-1 beta and accumulation of fibronectin and smooth muscle cells in the subendothelium (N. Clausell, S. Molossi, M. Rabinovitch, Am J Pathol 1993, 142, 1772-1786). Proteolytic enzymes including elastases regulate cytokine activity and are associated with the development of neointimal proliferation. We now report ultrastructural evidence of elastolytic activity in the donor compared to host coronary arteries judged by a fivefold increase in the breaks in the internal elastic lamina, (P < 0.01) correlating with a 10-fold increase in elastase activity per mg tissue (P < 0.01). The enzyme activity is serine elastase, i.e., inhibited by phenylmethyl sulfonyl fluoride, and elafin but not EDTA. Using a novel strategy that greatly increases the activity extractable from the tissue, we resolved the enzyme on an elastin substrate gel as a protein of approximately 23 kd. Ours is the first report and characterization of increased elastase activity associated with the development of the post-cardiac transplant coronary arteriopathy. The source may be inflammatory or smooth muscle cells, and elastase may play a pathophysiological role in neointimal proliferation by activating cytokines and growth factors and by release of chemotactic peptides.

Animals↗
PubMed1993

The ductus arteriosus migratory smooth muscle cell phenotype processes tropoelastin to a 52-kDa product associated with impaired assembly of elastic laminae.

We established the identity of a 52-kDa protein secreted by fetal lamb ductus arteriosus (DA) smooth muscle cells (SMC) and suggest how it might be related to structural changes unique to DA development, i.e. reduced assembly of elastic laminae and associated formation of intimal cushions. We produced a monoclonal antibody (HI-20) to the 52-kDa protein and observed, by electron microscopy, immunogold labeling of elastin in both DA and aorta vessel walls. Western immunoblotting showed that HI-20, as well as antibodies to tropoelastin, reacted with the 52-kDa protein secreted by DA SMC, as well as with 68-kDa tropoelastin. The highly specific antibody to the carboxyl-terminal sequence of tropoelastin failed, however, to recognize the 52-kDa protein, although it reacted well with the 68-kDa tropoelastin. Amino acid analysis and sequencing data confirmed the identity of the affinity-purified 52-kDa protein as truncated tropoelastin with an intact amino terminus. Cell-free translation of mRNA extracted from DA and aorta SMC produced a 68-kDa, but not a 52-kDa, immunoprecipitated tropoelastin. When DA and aorta SMC were pulsed with [14C]valine, we immunoprecipitated, after only a 15-min chase, both 68-kDa and 52-kDa tropoelastin from cell extracts of DA SMC, but only the 68-kDa tropoelastin was present in aorta SMC. There was no evidence of proteolytic degradation of radiolabeled aorta 68-kDa tropoelastin to a 52-kDa species when mixed with DA SMC conditioned medium. This suggests that the 52-kDa tropoelastin is the result of cell-associated processing or degradation of an original 68-kDa product of translation. Furthermore, pulse-chase experiments showed initial secretion of equivalent amounts of 68-kDa and 52-kDa tropoelastins by cultured DA SMC with increasing accumulation of the 52-kDa species, suggesting its impaired insolubilization. The production, in high concentration, of a 52-kDa tropoelastin product that lacks the carboxyl terminus, may prevent its alignment on the microfibrillar scaffold, resulting in abnormal assembly of elastic laminae in the DA. The accumulation of this soluble tropoelastin may be associated with the previously described property of chemotaxis resulting in the increased SMC migration into the subendothelium associated with DA intimal thickening.

Amino Acid Sequence↗
PubMed1993

Scimitar syndrome in infancy.

OBJECTIVES: The objectives of this study were to determine the anatomic and physiological factors most responsible for the severe symptoms and poor prognosis of infants with scimitar syndrome. BACKGROUND: Whereas the diagnosis of scimitar syndrome is often made incidentally in older children and adults who undergo chest radiography for diverse reasons, infants in whom the diagnosis is made typically present with severe symptoms and have a poor prognosis. METHODS: The clinical, catheterization and imaging data of 13 consecutive infants with scimitar syndrome who underwent cardiac catheterization in the 1st 6 months of life were reviewed, with emphasis on the pulmonary artery pressure, pulmonary and cardiovascular anatomy, therapeutic interventions and outcome. RESULTS: Twelve of the 13 infants had pulmonary hypertension at the time of diagnosis. Six patients died despite specific treatment. Eleven of 13 infants had associated cardiac malformations and 9 had large systemic arterial collateral channels to the right lung. Seven patients had anomalies involving the left side of the heart, especially varying degrees of hypoplasia of the left heart or aorta, and six of these patients died. Ten patients underwent surgical or transcatheter therapy in the 1st year of life. Systemic arteries to the right lung were ligated in three patients and occluded by transcatheter embolization in four. Balloon angioplasty was carried out in two patients, one with stenosis of the left-sided pulmonary veins and one with stenosis of the anomalous right pulmonary vein. The latter had placement of a balloon-expandable stent. In both patients, pulmonary vein stenosis progressed. Six patients had surgical repair of associated cardiovascular anomalies, and two required repair of extracardiac congenital anomalies. Occlusion of the anomalous systemic arteries was generally associated with clinical improvement, but congestive heart failure and pulmonary hypertension recurred in those patients with associated cardiovascular anomalies, whose condition subsequently responded after correction of the shunt lesions. CONCLUSIONS: The severe symptoms and pulmonary hypertension found in infants with scimitar syndrome have many causes. Anomalous systemic arterial supply, pulmonary vein stenosis and associated cardiovascular anomalies play a significant role, and the ultimate outcome of individual infants depends on the feasibility of treating these anomalies in early infancy.

Abnormalities, Multiple↗
PubMed1993

Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators.

OBJECTIVE: To describe the demographic and haemodynamic variables of children presenting with primary pulmonary hypertension or pulmonary hypertension appearing or persisting after surgical correction of congenital heart defects and to assess the acute effect of vasodilator drugs on their pulmonary vascular bed. DESIGN: Retrospective review. SETTING: Paediatric cardiology department and intensive care unit of a large tertiary centre. PATIENTS: Fourteen consecutive patients presenting with primary pulmonary hypertension (group 1) or pulmonary hypertension persisting or appearing late after complete surgical repair (group 2). INTERVENTION: Baseline haemodynamic measurements were taken in room air at rest and repeated in 100% oxygen. With constant monitoring of heart rate and pulmonary and systemic arterial pressures, patients were given serial intravenous, sublingual, or oral incremental doses of vasodilators (mean 4.1 trials per patient). The maximum effect of the drug was charted. MAIN OUTCOME MEASURES: A positive response to acute vasodilator tests was defined as a decrease in mean pulmonary or mean systemic arterial pressure > 15% with the mean pulmonary artery pressure not reaching the systemic level and either no change or an increase in mean systemic arterial pressure. Haemodynamic variables between groups (1 v 2, responders v non-responders, patients experiencing or not experiencing adverse effects to vasodilators) were compared by a two tailed unpaired Student's t test, and their survival curves were compared by the log rank statistic. RESULTS: Groups are small and definitive conclusions are difficult to draw, but the baseline haemodynamic assessments were not significantly different between group 1 and 2 or between responders and non-responders to vasodilators. Patients experiencing adverse effects had a higher pulmonary vascular resistance (p = 0.04) and wedge pressure (p = 0.02) than those without adverse effects. Of the vasodilators used, tolazoline, hydralazine, salbutamol, phentolamine, and phenoxybenzamine were ineffective. A positive response was seen in five of 13 patients given oxygen, in one of eight given prostacyclin, four of 12 given nifedipine, four of eight given diltiazem, one of six given captopril, and two of seven given glyceryl trinitrate. Estimates of survival of the population with primary pulmonary hypertension were 37% at one year and 12% at 2.5 years. Survival was significantly shorter in the non-responders than in the responders (p = 0.005). CONCLUSION: Children with primary pulmonary hypertension present to the cardiologist at a young age (five of eight were younger than 7 years) but with advanced pulmonary vascular disease and have a poor prognosis. 64% of group 1 and group 2 patients had a positive response to acute treatment with at least one vasodilator. Calcium channel blockers were the most effective agents. There was a positive response to drugs despite a negative response to acute treatment with oxygen. The survival of non-responders was shorter than that of the responders.

Adolescent↗
PubMed1993

The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase.

We and others have previously shown that a 67-kD cell surface elastin/laminin-binding protein (EBP) is responsible for cell adhesion to elastin and laminin and for mediating the process of elastin fiber assembly, but the nature of this protein was unknown. In this report we provide evidence that a 67-kD catalytically inactive form of beta-galactosidase produced by alternative splicing demonstrates immunological and functional similarity and sequence homology to the 67-kD EBP, suggesting that the two might be the same. Antibody prepared to a synthetic peptide, N-Ac-GSPSAQDEASPL, corresponding to a frame-shift-generated sequence unique to the alternatively spliced form of human beta-galactosidase, also recognized sheep EBP both on Western blotting and in aortic tissue. Furthermore, this synthetic peptide (S-GAL) binds to elastin and laminin, but not to fibronectin, collagen I, or collagen III. Moreover, both tropoelastin and laminin which bind to S-GAL peptide affinity columns can be specifically eluted from them with an excess of free S-GAL peptides. In addition, sequence homology among this splice variant of human beta-galactosidase, sheep EBP, and NH2-terminal sequences of some elastases suggests that these proteins share a common ligand-binding motif that has not been previously recognized.

Alternative Splicing↗
PubMed1993

Upregulation of fibronectin synthesis by interleukin-1 beta in coronary artery smooth muscle cells is associated with the development of the post-cardiac transplant arteriopathy in piglets.

We previously described in piglets after heterotopic cardiac transplantation the early development of a coronary arteriopathy characterized by increased immunostaining for fibronectin and interleukin-1 beta (IL-1 beta) in the vessel wall. The objective of this study was to culture smooth muscle cells from donor and host coronary arteries in these piglets to determine whether donor cells produce more fibronectin than host cells as judged by increased protein and mRNA levels, and whether IL-1 beta may be regulating this increase by an autocrine mechanism involving increased production of the cytokine. We documented increased donor coronary artery smooth muscle cell fibronectin protein synthesis and mRNA compared to host. By using neutralizing antibodies to IL-1 beta, fibronectin protein synthesis and mRNA levels were reduced in donor cells to the levels observed in the host cells and a similar reduction in synthesis was observed with the IL-1 receptor antagonist. Immunoprecipitation of newly synthesized IL-1 beta revealed increased endogenous levels in donor compared to host cells. We therefore suggest in the coronary arteriopathy a pathophysiologic mechanism whereby IL-1 beta-mediated increased fibronectin synthesis may promote lymphocyte trapping and migration of medial smooth muscle cells leading to progressive intimal thickening associated with the post-cardiac transplant coronary arteriopathy.

Animals↗
PubMed1993

Regulation of fetal lamb ductus arteriosus smooth muscle cell migration by indomethacin and dexamethasone.

Postnatal closure of the ductus arteriosus (DA) requires the development, during late gestation, of "intimal cushions." These structures, which partially occlude the vessel lumen, are characterized by smooth muscle cell (SMC) migration into an expanded subendothelium. DA SMC migration is dependent upon increased fibronectin (FN) production. We hypothesized that indomethacin (INDO) or dexamethasone, which could influence FN production, may affect SMC migration and DA intimal cushion formation. SMC harvested from the DA and aorta of 100-d fetal lambs were seeded onto three-dimensional collagen gels. Migration into the gels was quantitatively assessed by phase-contrast microscopy. INDO retarded DA SMC migration (p < 0.05), but it had no effect on aorta SMC migration. Synthesis of FN was measured after [35S]-methionine radiolabeling of cells, gelatin sepharose extraction of conditioned media, and resolution by SDS-PAGE. Despite the decrease in migration, INDO did not affect FN synthesis in DA SMC, whereas dexamethasone, a stabilizer of FN mRNA that increased DA FN synthesis by 44%, had no further effect on SMC migration. We then investigated whether INDO might be influencing SMC migration by decreasing collagenase production or altering cell shape through changes in F-actin polymerization. Collagenase activity, assessed by zymography using collagen types I and IV, was similar in control and treated DA and aorta cells. Image analysis of the actin cytoskeleton after rhodamine-phalloidin staining of DA SMC, however, revealed significant shortening of INDO-treated DA SMC relative to control, consistent with the observed reduction in migration.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

Relative efficiency of incorporation of newly synthesized elastin and collagen into aorta, pulmonary artery and pulmonary vein of growing pigs.

It is generally accepted that, once laid down in the extracellular matrix, elastin turns over only very slowly if at all. However, much of the evidence for minimal turnover of elastin comes from aortic tissue. In this study we have compared the relative synthesis rates of elastin and collagen with their relative accumulation rates in segments of aorta (AO), pulmonary artery (PA), and pulmonary vein (PV) of young, growing pigs. While rates of elastin synthesis are comparable in the AO and PA, the PA accumulates only 33% of the elastin deposited in the AO. Similarly, while the rate of elastin synthesis in the PV is 60% of that in the AO, accumulation of elastin is only 20% of that in the AO. Similar discrepancies between collagen synthesis and accumulation were seen among these three vessels. These data suggest that, at least in growing animals, the efficiency of permanent incorporation of elastin and collagen into the extracellular matrix may be an important factor in determining the final contents of these connective tissue proteins in vascular tissues.

Aging↗
PubMed1993

A developmentally regulated program restricting insolubilization of elastin and formation of laminae in the fetal lamb ductus arteriosus.

BACKGROUND: The ductus arteriosus (DA) is a fetal vessel in which the elastic laminae fail to assemble normally in late gestation. This feature is associated with the development of intimal cushions, structures that partially occlude the DA lumen and assure that the vessel will close completely when it constricts postnatally. EXPERIMENTAL DESIGN: We studied the fetal lamb DA at two different gestational time-points, 100 days before, and 138 days coincident with intimal cushion formation (term = 145 days) to establish the ultrastructural basis for the 'disassembly' of elastic laminae apparent on light microscopy and to determine further whether the mechanism was due to increased elastolytic activity, decreased synthesis of tropoelastin, or impaired insolubilization of tropoelastin. RESULTS: Morphometric ultrastructural analyses of tissue from the 138-day gestation fetal lambs revealed that the volume density of elastin in the DA vessel wall was only 40% of that in the aorta (Ao) and 50% of that in the pulmonary artery (PA). Moreover, only 16% of the elastin present contributed to the formation of laminae when compared to 80% in the Ao and 50% in the PA. Despite the morphologic appearance of 'fragmented' elastin, there was no evidence of increased elastolytic activity in the DA at either gestational time-point as judged by solubilization of a [3H] elastin substrate. The reduced elastin apparent was morphologically accompanied by an increase in soluble (tropo) elastin in DA compared with Ao and PA, as measured by enzyme linked immunosorbent assay, in tissue from both 100- and 138-day gestation lambs. Lack of differences in tropoelastin mRNA levels when comparing the 3 vessels suggested that the enzyme linked immunosorbent assay measurements reflected increased DA tropoelastin accumulation owing to lack of insolubilization rather than an increase in synthesis. Reduced insolubilization of newly synthesized elastin was evident in the DA compared with the Ao at 100 days gestation and in the DA compared with both Ao and PA at 138 days gestation in association with reduced desmosine levels. CONCLUSIONS: The mechanism of the decrease in tropoelastin insolubilization was unrelated to lysyl oxidase activity in the tissue and represents a unique developmental program.

Animals↗
PubMed1993

Coronary artery endothelial interleukin-1 beta mediates enhanced fibronectin production related to post-cardiac transplant arteriopathy in piglets.

BACKGROUND: Graft coronary arteriopathy has become the major complication observed in the late follow-up of cardiac transplant patients. We investigated this process experimentally in piglets after a heterotopic cardiac transplant and observed early changes in donor coronary arteries compatible with an immune-inflammatory process, ie, there is increased expression of interleukin-1 beta (IL-1 beta), fibronectin, and activated lymphocytes associated with intimal thickening. METHODS AND RESULTS: In this study, we cultured porcine coronary artery endothelial cells from host and donor hearts and found similarities in morphology and uptake of acetylated low-density lipoprotein (LDL). As well, host and donor cells showed similar patterns of growth, protein, and glycosaminoglycan synthesis. Endothelial cell fibronectin synthesis was determined after radiolabeling with [35S]-methionine in serum-free medium, gelatin-sepharose extraction of the culture medium and resolution on 5% SDS-PAGE. Donor coronary artery endothelial cell fibronectin synthesis was up to fivefold higher than that of host but was not associated with comparable increased levels of fibronectin mRNA. IL-1 beta appeared to mediate this enhanced fibronectin production, since the IL-1 receptor antagonist caused a 50% decrease in this feature, a change not observed in host cells. Furthermore, donor endothelial cells produced twice the amount of IL-1 beta compared with host cells as judged by immunoprecipitation. CONCLUSIONS: Increased donor coronary artery endothelial cell fibronectin appears to be regulated at least partly by an autocrine mechanism involving IL-1 beta, and fibronectin may mediate lymphocyte trafficking and smooth muscle cell migration related to graft arteriopathy.

Animals↗
PubMed1993

Pulmonary vascular obstructive disease.

The history, clinical course, pathophysiology, pathology, diagnosis, and therapy of pulmonary vascular obstructive disease are presented. An explanation is provided for the terms Eisenmenger syndrome, Eisenmenger complex, and pulmonary vascular disease. The complications frequently seen in the natural history of the condition are presented, as are the therapeutic options. Despite intensive investigation of new therapeutic products, the most promising treatment for established pulmonary vascular obstructive disease remains heart-lung operation or single-lung transplant with repair of cardiac defects. Even with this option, the long-term outlook for this progressive condition remains dismal.

Arterial Occlusive Diseases↗
PubMed1993

Hyperplasia of pulmonary arterial media in infantile familial pulmonary hypertension associated with severe metabolic acidosis.

Two female siblings, offspring of consanguinous parents, died at 10 and 12 wk of age following short illnesses characterized clinically by hypoxia and severe metabolic acidosis. Cardiac catheterization confirmed severe pulmonary hypertension in the second infant, who survived 6 wk after onset of symptoms and 4 wk after admission to hospital; extensive investigations failed to identify any inborn metabolic error. At autopsy, small pulmonary arteries/arterioles in both cases showed marked medial thickening due to smooth muscle hyperplasia; concentric intimal fibrosis was present focally in the older infant. Compared morphometrically with small pulmonary arteries in 20 infantile controls who died of Reye's syndrome (n = 8), a Reye's-like illness (n = 5) or an identified metabolic error associated with metabolic acidosis (n = 7), intraacinar pulmonary arteries in both cases, were significantly more numerous and had a significantly greater relative medial thickness. We suggest that an autosomal recessive gene caused or potentiated the pulmonary medial hyperplasia. The latter finding, compared with medial hypertrophy, is rarely described as the morphologic basis of pulmonary hypertension, and its occurrence may be restricted to early infancy. In this family, the relationship between hypertensive pulmonary arteriopathy and severe metabolic acidosis remains speculative.

Acidosis↗
PubMed1993

Increased interleukin-1 beta and fibronectin expression are early features of the development of the postcardiac transplant coronary arteriopathy in piglets.

The mechanism causing intimal thickening in the postcardiac transplant coronary arteriopathy (PCTCA) is associated with interactions between inflammatory cells and vascular cells. Our previous studies related intimal thickening to fibronectin-dependent smooth muscle cell (SMC) migration into the subendothelium, and others have shown that cytokines, eg, interleukin (IL)-1 beta, up-regulate SMC fibronectin synthesis. In this study, we identified, in piglets, features compatible with early development of the PCTCA. Ultrastructure revealed increased SMC and inflammatory cells in the subendothelium. Immunohistochemistry showed major histocompatibility complex II presentation in the endothelium and adventitia, associated with infiltration of different subsets of inflammatory cells; increased IL-1 beta, particularly in the endothelium; and fibronectin, in the subendothelium and inner media, the latter confirmed by quantitative immunoelectron microscopy. In the PCTCA, increases in IL-1 beta and fibronectin could mediate adherence, transendothelial migration and trapping of inflammatory cells, and SMC migration into the subendothelium.

Animals↗