Large Elastic Arteries Research Articles

Collagen-targeted antibodies inhibit platelet-dependent thrombosis in vivo

Subendothelial collagen is one of the main triggers of platelet-dependent thrombus formation in arteries. The antithrombotic effects of rabbit polyclonal inhibitory antibodies to rat collagen type I-III and of murine non-inhibitory monoclonals to human recombinant single-/two-chain urokinase-type plasminogen activator (rscu-/rtcu-PA), cross-reacting with rat scu-/tcu-PA and their chemically synthesized conjugate, were studied both in vitro and in vivo. Anticollagen antibodies and bispecific conjugate inhibited human platelet adhesion, aggregation and formation of thrombus-like structures induced by rat collagen immobilized on the polystyrene surface in a condition mimicing a high shear rates in the large elastic arteries. Monoclonals to human rscu-/rtcu-PA did not block the collagen-induced platelet activation in vitro. The short-term treatment of the collagen-soaked silk thread by the collagen antibodies suppressed the platelet-dependent thrombus formation in the arterio-venous shunt in rats by 56 ± 4% (P<0.05). Bispecific conjugate, directed to collagen and endogenous rat scu-/tcu-PA 1inhibited thrombus formation by the same factor as anticollagen antibodies. The treatment of collagen-adsorbed conjugate by human rtcu-PA did not increase the antithrombotic effect. The present results suggest, that the local administration of the anticollagen antibodies to the site of vascular injury can be an efficient tool for prophylaxis of platelet-dependent thrombus formation in arteries at thrombolysis or percutaneous transluminal coronary angioplasty.

Equipment and technique forIn vitro modeling of thrombogenesis

The device is a centrally oriented rotary magnetic disk producing a certain clearance between the rotary part and the collagen-coated bottom of a standard multiwell plate. Regulation of the speed of rotation makes it possible to reproduce the high shear rates characteristic for large elastic arteries.

The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis

To identify genes involved in vascular disease, we investigated patients with supravalvular aortic stenosis (SVAS), an inherited vascular disorder that causes hemodynamically significant narrowing of large elastic arteries. Pulsed-field gel and Southern analyses showed that a translocation near the elastin gene cosegregated with SVAS in one family. DNA sequence analyses demonstrated that the translocation disrupted the elastin gene and localized the breakpoint to exon 28. Taken together with our previous study linking SVAS to the elastin gene in two additional families and existing knowledge of vascular biology, these data suggest that mutations in the elastin gene can cause SVAS.

The relationship between wall tension, lamellar thickness, and intercellular junctions in the fetal and adult aorta: Its relevance to the pathology of dissecting aneurysm

It is known that the distribution of stress and strain in the vessel wall is not uniform. We believe that this explains the location of the plane of dissection in dissecting aneurysms of large elastic arteries. We have investigated the effects of non-uniformity of stress and strain on the thickness of each elastic lamella and on the distribution of intercellular junctions in the media of developing and adult rats, to seek evidence to support this hypothesis. Intercellular junctions were identified by transmission electron microscopy of whole wall sections. A morphometric study of elastic tissue distribution was made on an image analysis computer. Differences were analysed using one-way analysis of variance. There are between six and eight elastic lamellae in the aorta of rats. In the fetus, only the internal elastic lamella is complete; the others were not fully formed by term. In the adult, the inner five elastic lamellae were thicker than the remaining two or three, and smooth muscle cells in the thicker lamellar units had more cell-cell contacts of all types examined. These data support the concept of a difference in stress-resisting properties of the aortic wall on the junctions between the inner two-thirds and the outer third of the media. The findings indicate that, as proposed in theoretical models the innermost lamellae support the high tension. In the adult aorta, the structure is modified to enhance the capacity to resist stress in the internal two-thirds of the media.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular involvement in sarcoidosis: A report of 40 autopsy cases

We examined pulmonary vascular involvement in 40 autopsy cases of sarcoidosis. In these cases granulomatous involvement was observed at all levels from large elastic pulmonary arteries to venules, and venous involvement was more prominent than arterial involvement. The extent of granulomatous vascular involvement was related to that of parenchymal granuloma. No significant difference was found between upper and lower lobes in the incidence of granulomatous vascular involvement. The distribution of granulomata in the blood vessels was segmental and adventitial, and medial involvement was prominent in the larger vessels. Healed lesions of granulomatous vascular involvement also were observed at various levels in blood vessels. Prominent granulomatous involvement was found in the lymphatic capillaries and collecting lymphatic vessels in lungs with sarcoidosis. Serial sections of the lungs demonstrated interstitial granuloma directly connecting the lymphatic capillaries around small blood vessels. Granulomatous involvement in vasa vasorum and lymphatic capillaries is likely to be an important factor in the pathogenesis of granulomatous vascular involvement in lungs with sarcoidosis. The present study suggests that granulomatous vascular involvement and its sequelae may contribute to the development of pulmonary sarcoidosis.

Bromodeoxyuridine labeling and DNA content of pulmonary arterial medial cells from hypoxia-exposed and nonexposed healthy calves

SUMMARY Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo dna synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total dna content in medial cells from control (pulmonary arterial pressure = 32 ± 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 ± 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P &lt; 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia-exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of dna content by flow cytometry indicated a decrease (P &lt; 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and dna content of cells from the pulmonary arteries of hypoxia-exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of dna synthesis and subsequent cell division. Results are suggestive of smooth muscle cell hyperplasia in the vascular media of hypoxia-exposed calves.

Transforming growth factor-beta 1 is decreased in remodeling hypertensive bovine pulmonary arteries.

The development of pulmonary hypertension in hypoxic newborn calves is associated with a complex pattern of increased tropoelastin and type I procollagen synthesis and deposition by smooth muscle cells in large elastic pulmonary arteries compared to normoxic controls. We examined the possibility that transforming growth factor-beta 1 (TGF-beta 1) may be associated with the production of extracellular matrix protein in this model of pulmonary hypertension. Medial smooth muscle cells in both normotensive and hypertensive vessels, as assessed by immunohistochemistry, were the major source of TGF-beta 1. Staining was confined to foci of smooth muscle cells in the outer media and appeared greater in normotensive than hypertensive vessels. Consistent with the immunohistochemistry, a progressive, age-dependent increase in normotensive pulmonary artery TGF-beta 1 mRNA was observed after birth, whereas TGF-beta 1 mRNA remained at low, basal levels in hypertensive, remodeling pulmonary arteries. These observations suggest that local expression of TGF-beta 1 is not associated with increased extracellular matrix protein synthesis in this model of hypoxic pulmonary hypertension.

Outward currents in rabbit pulmonary artery cells dissociated with a new technique

Single cells from the rabbit pulmonary artery were isolated using a new and convenient procedure. Strips of muscle were incubated overnight in papain at 6 degrees C and dispersed the following morning after warming the tissue for 10 min. This method consistently produced a high yield of relaxed cells, which reversibly responded to vasoconstrictors and remained viable for many hours. The electrophysiological properties of these cells were studied using the patch-clamp technique in the whole-cell configuration. In physiological Ca2+ solution with K(+)-filled pipettes, cells had a high input resistance (approximately 17 G omega) and an average resting potential of -55 mV. In voltage clamp, several components of outward current could be identified. Depolarizing voltage steps revealed a prominent, transient current (Itran), having extremely rapid activation (less than 5 ms) and inactivation (less than 15 ms) kinetics. Itran was followed by a more slowly activating current (IKso) that was sustained over 100 ms. Both currents were essentially abolished by a 4-aminopyridine (4-AP) and sensitive to Ca2+ influx. IKso, but not Itran, was blocked by tetraethylammonium (TEA) and had the properties of a Ca(2+)-activated K+ current. Holding the membrane potential at -40 mV completely inactivated Itran and unmasked a time-independent, background current superimposed on IKso. The background current was also blocked by 4-AP. In addition, when adenosine triphosphate (ATP), but not guanosine triphosphate (GTP), was omitted from the patch-pipette, spontaneous bursts of outward current (SOCs) were superimposed on the voltage-activated currents. However, since SOCs were rarely observed when ATP and GTP were present together, they are unlikely to be active under physiological conditions. Thus at least four types of outward current can be distinguished in isolated rabbit pulmonary artery cells. These include a novel transient current which could be activated from the resting potential. It activates much more rapidly than outward currents previously reported in vascular muscle, and would rapidly oppose action potential firing. This current could therefore be responsible for the inability of large elastic arteries to fire action potentials.

Pulmonary arterial dissections and ruptures: To be considered in patients with pulmonary arterial hypertension presenting with cardiogenic shock or sudden death

Four unusual cases of sudden death due to pulmonary arterial hypertension complicated by dissection and/or rupture of the main pulmonary artery are reported. The patients, 3 males and 1 female, ranged from 17 to 77 years old. Each had chronic pulmonary arterial hypertension, marked pulmonary arterial dilation and degenerative medial changes of the large elastic pulmonary arteries. The first patient had a partial thickness tear of the main pulmonary artery with local dissection without external rupture and died of shock. The other three patients died after external rupture of the main pulmonary artery, based on a full thickness tear in one case, a small dissection in another and extensive dissection in the third. In the setting of pulmonary arterial hypertension, dissection, rupture, or dissection and rupture of the pulmonary artery should be considered in the differential diagnosis when patients present in cardiogenic shock or with sudden death.

Brief overview of the mounting evidence that atherosclerosis is both preventable and reversible.

The major life-threatening events in advanced atherosclerosis are precipitated by the plaque. Thrombosis in the muscular arteries and rupture of the large elastic arteries usually follows rupture of the plaque's fibrous cap. The smooth muscle cell (SMC) participates in many aspects of the atherosclerotic process: lipid uptake, synthesis of plaque components, and cell proliferation. The latter is a particularly significant aspect of the disease. High serum cholesterol levels stimulate proliferation of arterial medial cells; low-density lipoproteins (LDL) from hyperlipidemic plaques induce ingress and storage of cholesterol ester. These effects are inhibited by high-density lipoproteins (HDL). Endothelial injury may be an important part of the pathogenesis of some atherosclerotic plaques because powerful growth factors actively stimulate SMC proliferation, even when other risk factors are absent. Utilization of animal models of atherosclerosis, especially nonhuman primate models, has led to great progress in understanding this disease process. In controlled feeding experiments, severe atherosclerosis has been produced in rhesus monkeys by means of a high fat, high cholesterol diet. Animals then placed on a low fat, low cholesterol diet, or given cholestyramine, or a combination of these two approaches, showed a remarkable decrease in the size of their atherosclerotic plaques. Many epidemiologic studies, as well as more recent prospective intervention studies involving bile acid sequestrants, indicate by imaging techniques that plaque regression takes place in humans.

Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies.

Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.

Comparative toxicity of the cardiovacular toxin allylamine to porcine aortic smooth muscle and endothelial cells

This study supports a recent hypothesis that the cardiovascular toxin, allylamine, is toxic to smooth muscle cells of large elastic arteries (aorta). Cultures of the porcine aortic smooth muscle, endothelial, and fibroblastic cells were exposed to varying concentrations of allylamine ranging from 5 μM to 340 μM. Monitored cytotoxic and cytolytic activities demonstrated that final concentrations of 60 μM allylamine decreased cell population viability of smooth muscle cells as much as 50%. Viability decreased approximately linearly with increasing concentrations of allylamine including spontaneous lysing of smooth muscle cells at 90 μM. Endothelial cells were more resistant to lower concentrations of allylamine requiring 90 μM to decrease cell population viability by 50%. In contrast, fibroblastic cells were very resistant to lower concentrations of allylamine. The specific lytic response of these cells in culture, measured by release of [ 3H]thymidine, gave findings parallel to the viability studies, i.e. at 100 μM allylamine smooth muscle cells demonstrated 75% specific lysis while endothelial cells showed 29%. Growth studies of cells surviving an 8-h exposure to allylamine indicate that surviving endothelial cells have better growth characteristics than surviving smooth muscle cells; both cell lines are also apparently injured at concentrations of allylamine much lower than the CT 50. These studies show that of the cellular components of the vascular wall, smooth muscle cells appear to be the most sensitive to the toxic effects of allylamine.

Neuropeptide Y-like immunoreactivity in perivascular nerve fibres of the guinea-pig.

The distribution of perivascular nerve fibres displaying neuropeptide Y-like immunoreactivity was studied in the guinea-pig. Generally, neuropeptide Y fibres were numerous around arteries and moderate in number around veins. In the heart, immunoreactive fibres were numerous in the auricles and the atria (epi- and endocardium) whereas the ventricles had a more scarce supply. The coronary vessels were richly supplied with fibres. Around large elastic and muscular arteries the fibres formed well developed plexuses. Small arteries in the respiratory tract, the gastrointestinal tract and the genito-urinary tract received a particularly rich supply. In the liver, spleen and kidney only few perivascular fibres were seen. Since immunoreactive fibres around blood vessels disappeared upon surgical or chemical sympathectomy, and sequential immunostaining with antisera against dopamine-beta-hydroxylase (a marker for adrenergic neurons) and against neuropeptide Y revealed their co-existence, it is concluded that neuropeptide Y fibres around blood vessels are sympathetic and adrenergic.

Autoradiographic Analysis of Cell Proliferation and Protein Synthesis in the Pulmonary Trunk of Rats during the Early Development of Hypoxia-Induced Pulmonary Hypertension

The results of this study indicate that both cell proliferation and increased synthesis of extracellular matrix protein contribute to hypertrophy of the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension. As determined by autoradiography after 3H-thymidine injection, pulmonary hypertension results in increased labelling in all cell compartments of the pulmonary trunk wall, the most dramatic response occurring in the adventitia following 3 days' hypoxic exposure. Autoradiography also demonstrated differences in the degree of incorporation of 3H-proline into extracellular protein between hypoxic (3 and 21 days) and control rats. The major focus of 3H-proline incorporation shifted from the adventitia at 3 days to the tunica media at 21 days, although incorporation was significantly higher at 3 compared to 21 days in all wall compartments. The patterns of hyperplasia and matrix protein synthesis in the extrapulmonary arteries of the rat, as reported here, are distinctly different from those seen in many large elastic arteries during development of systemic hypertension. For example, the hyperplastic response of arterial vessels follows a similar temporal sequence in pulmonary and systemic hypertension. However, the adventitia is the region of the pulmonary trunk with highest cell proliferation in pulmonary hypertension while the media is most affected by systemic hypertension. The relevance of the changing patterns of cell proliferation and protein synthesis in the wall of the pulmonary trunk of chronically hypoxic rats to the structural and biochemical properties of this vessel during the early development of pulmonary hypertension is discussed.

A rapid digestive technique to expose networks of vascular elastic fibers for SEM observation.

The NaOH sonication digestion technique permits rapid isolation and exposure of intact networks of elastic fibers in vascular tissue for 3-dimensional observation with the SEM. The configuration of the network of elastic fibers within the vascular wall of large elastic arteries (aorta) is generally agreed to be a flexible framework through which smooth muscle cells and collagenous fibers are interwoven. However, the configuration of elastic fiber networks in muscular arteries, medium sized veins and smaller vessels remains unknown. When the lengthy standard biochemical elastin purification techniques were applied to vessels containing lesser amounts of elastic tissue and finer elastic fibers, the vessels were completely digested. In contrast, the digestion and sonication technique isolated and exposed intact networks of delicate elastic fibers in blood vessels which do not contain large amounts of elastic tissue. Unfixed vessels were cut into short segments, placed in 0.5 N NaOH and sonicated for 20-40 min. The specimens were rinsed in deionized distilled H2O, then autoclaved for 30 min. The tissue was rinsed a second time, fixed and processed routinely for SEM. Elastic stains and enzymatic digestion with chromatographically purified elastase and collagenase confirmed that the digestion and sonication technique produced clean, isolated networks of elastic fibers. Knowledge of the configuration of the networks of elastic fibers in different vessels enhances understanding of distensibility characteristics of individual vessels and serves as a baseline for studying alterations in the elastic framework which occur during aging and disease processes such as atherosclerosis, arterial hypertension and aneurysms.

Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats.

Structural changes of three categories of mesenteric arteries (representing elastic, muscular and arteriolar vessels) from 10- to 12-week-old and 28-week-old spontaneously hypertensive rats (SHR) were studied morphometrically at the light microscope level, and the results compared with age-matched Wistar-Kyoto normotensive rats. In 10- to 12-week-old SHR, hypertrophy of the vessel wall occurred only in the muscular and arteriolar vessels. At 28 weeks, further thickening of the vessel wall occurred in the muscular and arteriolar vessels, and the superior mesenteric artery (elastic vessel) was also thickened in the SHR. There was no evidence that the wall of the relaxed hypertrophied vessels encroached upon the lumen of the vessel. The structural basis for the increase in the vessel wall thickness varied with vessel type. In the superior mesenteric artery, increase in the media at 28 weeks of age would be consistent with hypertrophy of the smooth muscle cells. In the large muscular arteries, at 10-12 weeks of age, increase in medial mass occurred with increase in the number of the smooth muscle cell layers whereas at 28 weeks further increase in media could be due to hypertrophy of the smooth muscle cells. In the small arteriolar vessels, medial enlargement was due at all ages to an increase in the number of smooth muscle layers. Our results show that in the SHR hypertrophy of the media occurs not only in the small arteriolar vessels, but also in large elastic and muscular arteries.

Development and ageing of perivascular adrenergic nerves in the rabbit. A quantitative fluorescence histochemical study using image analysis

Age-related changes in vascular adrenergic nerves of 5 contrasting arteries in the rabbit were studied from before birth through to old age. Adrenergic nerves were demonstrated on stretch preparations using glyoxylic acid fluorescence histochemistry. Quantitative estimates of the densities of nerve fibres and varicosities were obtained by automated light microscopic image analysis. The early stages of development of vascular innervation were similar in all the vessels studied. They consisted of a period of outgrowth of axons; a period of rapid increase in density and formation of varicosities; and a later period of more gradual nerve growth. The timing of these stages varied greatly between the different vessels. The larger vessels, i.e. the carotid, renal and femoral arteries, had a well-developed innervation at birth, whilst the innervation of the smaller mesenteric and basilar arteries was sparse. Nerve loss occurred between 6 weeks and 6 months in the femoral artery and in old age (3 years or over) in the renal and carotid arteries. The large elastic arteries were, in general, more densely innervated than the smaller muscular arteries throughout life. The innervation of the different vessels became increasingly diverse between birth and adulthood, indicating a relationship between the pattern of vascular innervation and local physiological requirements. Factors which could influence age-related changes in nerve pattern and density are discussed.

Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs

Substance P-like immunoreactivity was localized by an indirect immunohistochemical technique in whole mounts and sections of blood vessels from the guinea-pig. There was a widespread association of nerve fibres that had substance P-like immunoreactivity with blood vessels, extending into all vascular beds. The relative densities of supply of different vessels were assessed visually and a rating scale used to compare them. Large elastic arteries close to the heart had dense networks of immunoreactive nerves associated with them. The density decreased as more peripheral beds were approached, except that there was a particularly dense network of nerves with arteries of the splanchnic beds. Arteries to myocardial, central nervous system, renal, reproductive and skeletal muscle beds all had substance P-immunoreactive nerves associated with them to varying extents. The venae cavae near the heart were densely supplied, but there were few fibres with their more peripheral extensions. Some large veins (e.g. pulmonary, hepatic portal and superior mesenteric) had a few fibres with them, but veins of peripheral vascular beds had very few or no immunoreactive nerve fibres. Substance P-like immunoreactivity in vascular nerves was markedly reduced in guinea-pigs that were injected with capsaicin but was unaffected by the injection of 6-hydroxydopamine. It is concluded that the vascular substance P-immunoreactive nerves are likely to be of sensory origin.

The Ultrastructure of Autonomic Cholinergic Nerves and Junctions

Publisher Summary This chapter discusses the ultrastructure of autonomic cholinergic nerves and junctions. Cholinergic neurones are widely distributed in the autonomic nervous system. Terminal varicosities of cholinergic autonomic nerves contain a predominance of small agranular vesicles and a small number of large granular vesicles, which differ in some respect from those found in adrenergic nerves and from “large opaque vesicles” found in non-adrenergic, non-cholinergic “purinegric” or “peptidergic” nerves. In the gastrointestinal tract, some nerve profiles contain flattened agranular vesicles that may represent another type of cholinergic nerve; some profiles contain mixtures of small agranular vesicles and other vesicle types perhaps indicating co-transmitters. The chapter also describes a generalized model of the cholinergic neuromuscular junction, which emphasizes “en passage” release of transmitter from extensive terminal, varicose fibres and electrotonic spread of activity via “gap junctions” between neighboring smooth muscle cells within effector bundles. The minimum width of the junctional cleft between cholinergic varicosities and effector cells varies between 15-20 μm in densely-innervated tissues, such as vas deferens and iris and 1-2 pm in large elastic arteries. In densely innervated tissues, sub-synaptic cysternae in smooth muscle are often found at close neuromuscular junctions.

ISOLATED STENOSIS OF THE PULMONARY ARTERY BRANCHES : AN AUTOPSY CASE WITH REVIEW OF THE LITERATURES

A necropsy of a 21-year-old male with isolated stenosis of the pulmonary artery was presented. The pulmonary artery branches showed various fibrous thickening including atheromata and mural thrombi. Those findings appeared mostly in elastic and large muscular pulmonary arteries as well as in medium sized arteries, while the small arteries and arterioles remained in slight changes. Systemic large elastic arteries seemed to be small and showed atheromatous lesions similar to those of the main pulmonary arteries. Moreover, eight autopsy cases with pulmonary artery stenosis from the literature were shortly reviewed and some pathological findings as an aid for angiographic cardiovascular studies were discussed.