Progesterone modulates endothelium-dependent coronary vascular reactivity in SHR.

Although progesterone has the ability to promote dilation of vascular smooth muscle, its role in coronary circulation is still poorly characterized, especially in essential hypertension and in a model of endogenous deficiency of ovarian hormones. Thus, this study evaluated the effect of progesterone treatment on endothelium-dependent coronary vascular reactivity in hypertensive (SHR) and ovariectomized rats. Adult SHR aged 8-10 weeks were divided into: SHAM, Ovariectomized (OVX) and Ovariectomized + treatment with 2 mg/kg/day of progesterone for 15 days (OVX-P4). Coronary vascular reactivity was investigated using the modified Langendorff method. After stabilization, baseline coronary perfusion pressure (CPP) was recorded and vascular reactivity to bradykinin (BK, 0.1-1000 ng) were assessed before and after infusion, either individually or in combination, with Nω-nitro-l-arginine methyl ester (l-NAME), indomethacin or clotrimazole. Scanning electron microscopy was used for qualitative analysis of the endothelium. OVX and OVX-P4 groups had a higher baseline CPP compared to that of the SHAM group. BK was able to promote vasodilation in all groups. However, relaxation to BK was less pronounced in the OVX group when compared to SHAM, with architecture loss and areas of cell atrophy having been observed. Progesterone treatment prevented this injury. Perfusion with l-NAME induced greater damage to the SHAM group, while the use of indomethacin led to a significant reduction in the vasodilator response to BK in the OVX-P4 group. Taken together, our results show that progesterone modulates endothelium-dependent coronary vasodilation in SHR ovariectomized, preventing damage caused by ovarian hormonal deficiency through a mechanism that involves prostanoid pathway.

Changes of the coronary arteries and cardiac microvasculature with aging: Implications for translational research and clinical practice.

Aging results in functional and structural changes in the cardiovascular system, translating into a progressive increase of mechanical vessel stiffness, due to a combination of changes in micro-RNA expression patterns, autophagy, arterial calcification, smooth muscle cell migration and proliferation. The two pivotal mechanisms of aging-related endothelial dysfunction are oxidative stress and inflammation, even in the absence of clinical disease. A comprehensive understanding of the aging process is emerging as a primary concern in literature, as vascular aging has recently become a target for prevention and treatment of cardiovascular disease. Change of life-style, diet, antioxidant regimens, anti-inflammatory treatments, senolytic drugs counteract the pro-aging pathways or target senescent cells modulating their detrimental effects. Such therapies aim to reduce the ineluctable burden of age and contrast aging-associated cardiovascular dysfunction. This narrative review intends to summarize the macrovascular and microvascular changes related with aging, as a better understanding of the pathways leading to arterial aging may contribute to design new mechanism-based therapeutic approaches to attenuate the features of vascular senescence and its clinical impact on the cardiovascular system.

Intravascular cardiac lipoproteinosis: extrarenal manifestation of lipoprotein glomerulopathy.

Intracapillary lipoprotein thrombi are a distinct histopathologic finding described in the setting of lipoprotein glomerulopathy. The disease is associated with mutations in the apolipoprotein E gene and responds well to lipid-lowering treatments. Lipoprotein glomerulopathy is thought to primarily affect the kidneys, and lipoprotein thrombi have never been described in any other organ. Herein we present the first recognized case with extrarenal manifestations in the form of intravascular cardiac lipoprotein deposition.

Native Coronary Collateral Microcirculation Reserve in Rat Hearts.

Background We occasionally noticed that native collateral blood flow showed a recessive trend in the early stages of acute myocardial infarction in rats, which greatly interferes with the accurate assessment of native collateral circulation levels. Here, we sought to recognize the coronary collateral circulation system in depth, especially the microcirculation part, on this basis. Methods and Results In this study, we detected native collateral flow with positron emission tomography perfusion imaging in rats and found that the native flow is relatively abundant when it is initially recruited. However, this flow is extremely unstable in the early stage of acute myocardial infarction and quickly fails. We used tracers to mark the collateral in an ischemic area and a massive preformed collateral network was labeled. The ultrastructures of these collateral microvessels are flawed, which contributes to extensive leakage and consequent interstitial edema in the ischemic region. Conclusions An unrecognized short-lived native coronary collateral microcirculation reserve is widely distributed in rat hearts. Recession of collateral blood flow transported by coronary collateral microcirculation reserve contributes to instability of native collateral blood flow in the early stage of acute myocardial infarction. The immature structure determines that these microvessels are short-lived and provide conditions for the development of early interstitial edema in acute myocardial infarction.

Preclinical Evaluation of a Novel Sirolimus-Eluting Iron Bioresorbable Coronary Scaffold in Porcine Coronary Artery at 6 Months.

OBJECTIVES: The aim of this study was to investigate the operability, 6-month efficacy, and safety of the novel sirolimus-eluting iron bioresorbable coronary scaffold (IBS) system compared with a cobalt-chromium everolimus-eluting stent (EES) (XIENCE Prime stent) in porcine coronary arteries. BACKGROUND: Bioresorbable scaffolds have been considered the fourth revolution in percutaneous coronary intervention. However, the first-generation bioresorbable scaffold showed suboptimal results. METHODS: Forty-eight IBS and 48 EES were randomly implanted into nonatherosclerotic swine. The operability, efficacy, and safety of the IBS and EES were evaluated using coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, and histopathologic evaluation at 7, 14, 28, 90, and 180 days after implantation. RESULTS: The operability of the ultrathin IBS (∼70 µm) was comparable with that of the EES, except for its visibility. There was no statistically significant difference in area stenosis between the IBS and EES from 28 to 180 days. The IBS maintained its integrity up to 90 days without corrosion, while corrosion was observed in a few struts in 2 of 10 IBS at 180 days. The percentage of endothelialization of IBS was higher than that of XIENCE Prime stents within 14 days after implantation. The fibrin score was higher in the IBS group at 28 days but comparable with the EES group at 90 and 180 days. No scaffold or stent thrombosis was seen in either group. No abnormal histopathologic changes in scaffolded or stented vessel segments and 5 main remote organs were observed in either group. CONCLUSIONS: Preclinical results suggest that the novel IBS has comparable operability, mid-term efficacy, and safety with the EES, and its corrosion profile in porcine coronary arteries is reasonable, which could support initial clinical study of the IBS.

High thoracic sympathetic block improves coronary microcirculation disturbance in rats with chronic heart failure.

INTRODUCTION: Coronary microcirculation disturbance plays an important role in chronic heart failure (CHF). High thoracic sympathetic block (HTSB) is effective to treat CHF, but its impact on coronary microcirculation is unclear. METHODS: Forty male Wistar rats were subcutaneously injected with isoproterenol (340 mg/kg) for 2 days. Eight weeks later, 24 surviving rats were randomized to the CHF and HTSB groups and 10 rats were used as the control group. 50 µl of saline and ropivacaine (0.2%) were epidurally infused everyday in the CHF and HTSB group respectively. Four weeks later, echocardiography and pathological and ultrastructural examination, capillary histochemical staining and vascular endothelial growth factor (VEGF) immunohistochemical staining in left ventricular (LV) subendocardial myocardium were performed. RESULTS: Compared with the control group, LV dilation and dysfunction, myocardial focal necrosis, capillary spasm appeared in the CHF group. HTSB ameliorated LV dilation and dysfunction, myocardial necrosis and capillary spasm. Rats in the CHF group had less myocardial capillary density and more VEGF expression than in the control group (1591 ±â€¯99 vs. 1972 ±â€¯118/mm2, 0.62 ±â€¯0.13 vs. 0.33 ±â€¯0.10 optic density, all p < 0.05). Myocardial capillary density (1782 ±â€¯96/mm2) was more and VEGF expression (0.47 ±â€¯0.12 optic density) was less in the HTSB group than in the CHF group (all p < 0.05). CONCLUSION: HTSB improves coronary microcirculation disturbance in CHF, which may contribute to reversing myocardial remodeling and dysfunction. HTSB stimulates myocardial capillary growth independent of VEGF.

Haemodynamic stress-induced breaches of the arterial intima trigger inflammation and drive atherogenesis.

AIMS: Inflammatory mediators, including blood cells and their products, contribute critically to atherogenesis, but the igniting triggers of inflammation remain elusive. Atherosclerosis develops at sites of flow perturbation, where the enhanced haemodynamic stress could initiate the atherogenic inflammatory process due to the occurrence of mechanic injury. We investigated the role of haemodynamic stress-induced breaches, allowing the entry of blood cells in the arterial intima, in triggering inflammation-driven atherogenesis. METHODS AND RESULTS: Human coronary samples isolated from explanted hearts, (n = 47) displayed signs of blood entry (detected by the presence of iron, ferritin, and glycophorin A) in the subintimal space (54%) as assessed by histology, immunofluorescence, high resolution episcopic microscopy, and scanning electron microscopy. Computational flow dynamic analysis showed that intimal haemorrhagic events occurred at sites of flow disturbance. Experimental carotid arteries from Apoe deficient mice showed discrete endothelial breaches and intimal haemorrhagic events specifically occurring at the site of flow perturbation, within 3 days after the exacerbation of the local haemodynamic stress. Endothelial tearing was associated with increased VCAM-1 expression and, within 7 days, substantial Ly6G+ leucocytes accumulated at the sites of erythrocyte-derived iron and lipids droplets accumulation, pathological intimal thickening and positive oil red O staining. The formation of fatty streaks at the sites of intimal breaches was prevented by the depletion of Ly6G+ leucocytes, suggesting that the local injury driven by haemodynamic stress-induced breaches triggers atherogenic inflammation. CONCLUSION: Haemodynamic-driven breaches of the arterial intima drive atherogenic inflammation by triggering the recruitment of leucocyte at sites of disturbed arterial flow.

Method for Combined Observation of Serial Sections of Stented Arteries Embedded in Resin by Light Microscopy and Transmission Electron Microscopy.

We have developed a new method for obtaining information on whole tissues by light microscopy (LM) and ultrastructural features by transmission electron microscopy (TEM). This method uses serial sections of a stented artery embedded in resin. Stents were implanted in porcine coronary arteries in this study. The heart was perfusion fixed in a 2% paraformaldehyde and 1.25% glutaraldehyde mixed solution. The stented artery was then removed, fixed in 1% osmium, embedded in Quetol 651 resin, and sectioned serially. For LM, the black color of osmium was removed from the section by immersion in periodic acid and hydrogen peroxide after deplasticization. These sections were stained with hematoxylin and eosin and Elastica-Masson trichrome stain. For TEM, thin sections were re-embedded in Quetol 812 resin by the resupinate method and cut into ultrathin sections. A clear, fine structure was obtained, and organelles, microvilli, and cell junctions in the endothelium were easily observed. The combined observation of adjacent specimens by LM and TEM enabled us to relate histopathological changes in the millimeter scale to those in the nanometer scale.

Heart structure in the Amazonian teleost Arapaima gigas (Osteoglossiformes, Arapaimidae).

The fish heart ventricle has varied morphology and may have a specific morpho-functional design in species adapted to extreme environmental conditions. In general, the Amazonian ichthyofauna undergoes constant variations in water temperature, pH and oxygen saturation, which makes these species useful for investigations of cardiac morphology. Arapaima gigas, a member of the ancient teleost group Osteoglossomorpha, is one of the largest freshwater fish in the world. This species has a specific heart metabolism that uses fat as the main fuel when O2 supplies are abundant but also can change to glycogen fermentation when O2 content is limiting. However, no information is available regarding its heart morphology. Here, we describe the heart of A. gigas, with emphasis on the ventricular anatomy and myoarchitecture. Specimens of A. gigas weighing between 0.3 and 4040 g were grouped into three developmental stages. The hearts were collected and the anatomy analyzed with a stereomicroscope, ultrastructure with a scanning electron microscope, and histology using toluidine blue, Masson's trichrome and Sirius red stains. The ventricle undergoes morphological changes throughout its development, from the initial saccular shape with a fully trabeculated myocardium and coronary vessel restricted to the subepicardium (Type I) (group 1) to a pyramidal shape with mixed myocardium and coronary vessels that penetrate only to the level of the compact layer (Type II) (groups 2 and 3). The trabeculated myocardium has a distinct net-like organization in all the specimens, differing from that described for other teleosts. This arrangement delimits lacunae with a similar shape and distribution, which seems to allow a more uniform blood distribution through this myocardial layer.

Non-invasive characterization of coronary artery atherosclerotic plaque using dual energy CT: Explanation in ex-vivo samples.

PURPOSE: In this study non-calcified plaque composition is evaluated by Dual Energy CT (DECT). Energy Dispersive X-ray Spectroscopy (EDS) has been used to study the Plaque composition. An attempt has been made to explain the DECT results with EDS analysis. METHODS: Thirty-two ex-vivo human cadaver coronary artery samples were scanned by DECT and data was evaluated to calculate their effective atomic number and electron density (Zeff & ρe) by inversion method. Result of DECT was compared with pathology to assess their differentiating capability. The EDS study was used to explain DECT outcome. RESULTS: DECT study was able to differentiate vulnerable plaque from stable with 87% accuracy (area under the curve (AUC):0.85 [95% confidence interval {CI}:0.73-0.98}] and Kappa Coefficient (KC):0.75 with respect to pathology. EDS revealed significant compositional difference in vulnerable and stable plaque at p < .05. The weight percentage of higher atomic number elements like F, Na, Mg, S, Si, P, Cl, K and Ca was found to be slightly more in vulnerable plaques as compared to a stable plaque. EDS also revealed a significantly increased weight percentage of nitrogen in stable plaques. CONCLUSIONS: The EDS results were able to explain the outcomes of DECT study. This study conclusively explains the physics of DECT as a tool to assess the nature of non-calcified plaques as vulnerable and stable. The method proposed in this study allows for differentiation between vulnerable and stable plaque using DECT.

Polymer-free dual drug-eluting stents evaluated in a porcine model.

BACKGROUND: Although drug-eluting stents have dramatically reduced the rates of restenosis and target lesion revascularization, they are associated with stent thrombosis (ST), a catastrophic event likely due to delayed endothelialization and chronic inflammation caused by the polymer and the metal scaffolds. To increase the safety and efficacy of stents, polymer-free dual drug-eluting stents (DDES) have been developed. METHODS: A total 160 stents (Bare-metal stents (BMS), polymer-free probucol stents (PrES), sirolimus-eluting stents (SES) and DDES) were randomly implanted in the coronary arteries of 80 pigs. 14, 28, 90 and 191 days after implantation, QCA and OCT evaluations were performed in 20 pigs respectively, and the arteries were harvested for scanning electron microscope (SEM), histomorphology, histopathology analyses and for the relative expression of CD31, CD34 and CD133 on mRNA and protein levels. RESULTS: At the 14-day time point, there were significant differences in the strut rate coverage (p = 0.011), with greater coverage in the PrES than in the SES group (53.2%vs. 20.3%, p = 0.002). As well, there were no significant differences in the expression of CD31, CD34 and CD133 between groups in mRNA and protein level. CONCLUSIONS: DDES were as safe as BMS and SES, but they did not further improve the endothelialization of the stented coronary arteries in the porcine model.

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation.

Effects of freezing, fixation and dehydration on surface roughness properties of porcine left anterior descending coronary arteries.

BACKGROUND: To allow measurements of surface roughness to be made of coronary arteries using various imaging techniques, chemical processing, such as fixation and dehydration, is commonly used. Standard protocols suggest storing fresh biological tissue at -40°C. The aim of this study was to quantify the changes caused by freezing and chemical processing to the surface roughness measurements of coronary arteries, and to determine whether correction factors are needed for surface roughness measurements of coronary arteries following chemical processes typically used before imaging these arteries. METHODS: Porcine left anterior descending coronary arteries were dissected ex vivo. Surface roughness was then calculated following three-dimensional reconstruction of surface images obtained using an optical microscope. Surface roughness was measured before and after a freeze cycle to assess changes during freezing, after chemical fixation, and again after dehydration, to determine changes during these steps of chemical processing. RESULTS: No significant difference was caused due to the freeze cycle (p>0.05). There was no significant difference in the longitudinally measured surface roughness (RaL=0.99±0.39µm; p>0.05) of coronary arteries following fixation and dehydration either. However, the circumferentially measured surface roughness increased significantly following a combined method of processing (RaC=1.36±0.40, compared 1.98±0.27µm, respectively; p<0.05). A correction factor can compensate for the change RaCß=RaC1+0.46in RaC due to processing of tissue, Where RaCß, the corrected RaC, had a mean of 1.31±0.21µm. CONCLUSIONS: Independently, freezing, fixation and dehydration do not alter the surface roughness of coronary arteries. Combined, however, fixation and dehydration significantly increase the circumferential, but not longitudinal, surface roughness of coronary arteries.

Comparison of a Drug-Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3-Year Follow-Up.

BACKGROUND: Arterial Remodeling Technologies bioresorbable scaffold (ART-BRS), composed of l- and d-lactyl units without drug, has shown its safety in a porcine coronary model at 6 months. However, long-term performance remains unknown. The aim of this study was to evaluate the ART-BRS compared to a bare metal stent (BMS) in a healthy porcine coronary model for up to 3 years. METHODS AND RESULTS: Eighty-two ART-BRS and 66 BMS were implanted in 64 Yucatan swine, and animals were euthanatized at intervals of 1, 3, 6, 9, 12, 18, 24, and 36 months to determine the vascular response using quantitative coronary angiography, optical coherence tomography, light and scanning electron microscopy, and molecular weight analysis. Lumen enlargement was observed in ART-BRS as early as 3 months, which progressively increased up to 18 months, whereas BMS showed no significant difference over time. Percentage area stenosis by optical coherence tomography was greater in ART-BRS than in BMS at 1 and 3 months, but this relationship reversed beyond 3 months. Inflammation peaked at 6 months and thereafter continued to decrease up to 36 months. Complete re-endothelialization was observed at 1 month following implantation in both ART-BRS and BMS. Scaffold dismantling started at 3 months, which allowed early vessel enlargement, and bioresorption was complete by 24 months. CONCLUSIONS: ART-BRS has the unique quality of early programmed dismantling accompanied by vessel lumen enlargement with mild to moderate inflammation. The main distinguishing feature of the ART-BRS from other scaffolds made from poly-l-lactic acid may result in early and long-term vascular restoration.

Caveolin 2: a facultative marker of unfavourable prognosis in long-term patency rate of internal thoracic artery grafts used in coronary artery bypass grafting. Preliminary report.

OBJECTIVES: Intimal hyperplasia leading to graft failure in patients undergoing coronary artery bypass grafting (CABG) is related to vascular smooth muscle cells (SMCs) proliferation. SMCs respond to a variety of mediators, the most important of which is platelet-derived growth factor (PDGF). The platelet-derived growth factor-induced cellular response has been shown to be mediated by caveolins. The aim of this study was to analyze CAV1-3 expression in internal thoracic artery (ITA) grafts used in CABG and correlate their expression with graft occlusion. METHODS: Six hundred patients undergoing CABG with the use of ITA grafts between 2008 and 2014 were enrolled into this prospective study. CAV1-3 expression in the ITA grafts was analyzed prior to graft transplantation into the coronary circulation via immunohistochemistry. Estimated caveolins expression pattern was then correlated with the occurrence of ITA graft failure observed within 24-months of surgery. RESULTS: Thirty-four patients developed ITA graft failure (subgroup A) and 566 study participants presented no adverse events (subgroup B). CAV1 and CAV3 expression levels in SMCs of the tunica media of the ITA grafts did not differ between the study subgroups and were not associated with the risk of graft failure. CAV2 was expressed within SMCs of the ITA grafts in 94.1% of the patients from subgroup A and 2.5% from subgroup B, and its expression was associated with ITA graft occlusion observed within 24-months after CABG. CONCLUSIONS: CAV2 expression in SMCs of the tunica media in autologous ITA transplants might indicate the risk of graft failure.

Establishment of a Novel Mouse Model of Coronary Microembolization.

BACKGROUND: Coronary microembolization (CME) has been frequently seen in acute coronary syndromes and percutaneous coronary intervention. Small animal models are required for further studies of CME related to severe prognosis. This study aimed to explore a new mouse model of CME. METHODS: The mouse model of CME was established by injecting polystyrene microspheres into the left ventricular chamber during 15-s occlusion of the ascending aorta. Based on the average diameter and dosage used, 30 C57BL/6 male mice were randomly divided into five groups (n = 6 in each): 9 µm/500,000, 9 µm/800,000, 17 µm/200,000, 17 µm/500,000, and sham groups. The postoperative survival and performance of the mice were recorded. The mice were sacrificed 3 or 10 days after the surgery. The heart tissues were harvested for hematoxylin and eosin staining and Masson trichrome staining to compare the extent of inflammatory cellular infiltration and fibrin deposition among groups and for scanning transmission electron microscopic examinations to see the ultrastructural changes after CME. RESULTS: Survival analysis demonstrated that the cumulative survival rate of the 17 µm/500,000 group was significantly lower than that of the sham group (0/6 vs. 6/6, P = 0.001). The cumulative survival rate of the 17 µm/200,000 group was lower than those of the sham and 9 µm groups with no statistical difference (cumulative survival rate of the 17 µm/200,000, 9 µm/800,000, 9 µm/500,000, and sham groups was 4/6, 5/6, 6/6, and 6/6, respectively). The pathological alterations were similar between the 9 µm/500,000 and 9 µm/800,000 groups. The extent of inflammatory cellular infiltration and fibrin deposition was more severe in the 17 µm/200,000 group than in the 9 µm/500,000 and 9 µm/800,000 groups 3 and 10 days after the surgery. Scanning transmission electron microscopic examinations revealed platelet aggregation and adhesion, microthrombi formation, and changes in cardiomyocytes. CONCLUSION: The injection of 500,000 polystyrene microspheres at an average diameter of 9 µm is proved to be appropriate for the mouse model of CME based on the general conditions, postoperative survival rates, and pathological changes.

Nitric Oxide Releasing Coronary Stent: A New Approach Using Layer-by-Layer Coating and Liposomal Encapsulation.

The sustained or controlled release of nitric oxide (NO) can be the most promising approach for the suppression or prevention of restenosis and thrombosis caused by stent implantation. The aim of this study is to investigate the feasibility in the potential use of layer-by-layer (LBL) coating with a NO donor-containing liposomes to control the release rate of NO from a metallic stent. Microscopic observation and surface characterizations of LBL-modified stents demonstrate successful LBL coating with liposomes on a stent. Release profiles of NO show that the release rate is sustained up to 5 d. In vitro cell study demonstrates that NO release significantly enhances endothelial cell proliferation, whereas it markedly inhibits smooth muscle cell proliferation. Finally, in vivo study conducted with a porcine coronary injury model proves the therapeutic efficacy of the NO-releasing stents coated by liposomal LBL technique, supported by improved results in luminal healing, inflammation, and neointimal thickening except thrombo-resistant effect. As a result, all these results demonstrate that highly optimized release rate and therapeutic dose of NO can be achieved by LBL coating and liposomal encapsulation, followed by significantly efficacious outcome in vivo.

Ultrastructure features of coronary artery endothelium in bactrian camel (Camelus bactrianus) / Características ultraestructurales del endotelio de las arterias coronarias en el camello bactriano (Camelus bactrianus)

Vascular endothelium play an essential role in regulating endothelial functions by maintaining normal vascular tone, modulating hemostasis, and preventing thromobogenesis. The aim of present study was to reveal ultrastructure features of coronary artery endothelium in Bactrian Camels by means of scanning electron microscope (SEM) technology. The results showed that the endothelial cells distribute along the direction of blood flow. Their morphology and protuberant degree towards luminal surface vary for different parts of the coronary artery. The luminal surface of a.c oronaria sinistra and a. coronaria dextra was covered by impaired and intact endothelium, respectively. Platelets and leukocytes sticking to the endothelium were found.

Las células endoteliales de los vasos sanguíneos juegan un rol esencial en la regulación de las funciones endoteliales manteniendo el tono vascular, modulando la homeostasis y previniendo la trombogénesis. En la investigación se utilizó un microscopio electrónico de barrido, revelando las características estructurales de las células endoteliales de los vasos coronarios de los camellos bactrianos. Los resultados indican que las células endoteliales estaban distribuidas a lo largo de la dirección de flujo. En distintas partes de la arteria coronaria existen diferencias en el grado de proyección de la morfología y de la superficie de la cavidad de dichas células. La superficie luminal de la arteria coronaria izquierda y la arteria coronaria derecha estaban cubiertas por endotelio deteriorado e intacto, respectivamente. Se observó adhesión de leucocitos y plaquetas en la superficie de las células endoteliales.

Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists.

Candida glabrata (CG) is an opportunistic fungal pathogen that initiates infection by binding to host cells via specific lectin-like adhesin proteins. We have previously shown the importance of lectin-oligosaccharide binding in cardiac responses to flow and agonists. Because of the lectinic-oligosaccharide nature of CG binding, we tested the ability of CG to alter the agonist- and flow-induced changes in cardiac function in isolated perfused guinea pig hearts. Both transmission and scanning electron microscopy showed strong attachment of CG to the coronary endothelium, even after extensive washing. CG shifted the coronary flow vs. auricular-ventricular (AV) delay relationship upward, indicating that greater flow was required to achieve the same AV delay. This effect was completely reversed with mannose, partially reversed with galactose and N-acetylgalactosamine, but hyaluronan had no effect. Western blot analysis was used to determine binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors, and the results indicate that flow-sensitive CELM receptors, ANG II type I, α-adrenergic 1A receptor, endothelin-2, and VCAM-1 bind to CG. In addition, CG inhibited agonist-induced effects of bradykinin, angiotensin, and phenylephrine on AV delay, coronary perfusion pressure, and left ventricular pressure. Mannose reversed the inhibitory effects of CG on the agonist responses. These results suggest that CG directly binds to flow-sensitive CELM receptors via lectinic-oligosaccharide interactions with mannose and disrupts the lectin-oligosaccharide binding necessary for flow-induced cardiac responses.

Tissue factor is unregulated in microvascular endothelial cells of patients with heart failure.

AIMS: Several lines of evidence point to hypercoagulability as an important factor for heart failure (HF) pathogenesis. METHODS: We hypothesised that endothelial tissue factor (TF) expression reflects altered tissue haemostasis which is related to the severity of HF. Accordingly, we investigated TF expression in the biopsies of 60 patients with HF and 22 without HF. In addition, we assessed the relationship between endothelial TF expression and clinical markers of HF severity. RESULTS: The control subjects without HF presented absent or weak TF expression in few microvessels, while the endomyocardial biopsies of patients with HF, capillary vessels presented both weak and severe staining patterns by immunohistochemistry usually with regional distribution. This was collaborated by the immune electron microscopic study. The severe microvessel TF antigen expression was found in 11 (18.3%) patients with HF. The endothelial TF expression was inversely associated with left ventricular ejection fraction (r=-0.42, p=0.001) and positively with N-terminal brain natriuretic peptide (r=0.36, p<0.023), markers of HF severity. CONCLUSIONS: Regional upregulation of the TF in the capillary endothelial cells suggests local myocardial thrombogenicity. Furthermore, the relationship between endothelial TF and HF severity would be keeping in line with the hypothesis that an altered tissue haemostasis is most profoundly expressed in patients with severe HF. Weak TF expression found in several microvessels of the biopsy specimens patients without HF pathology might be potentially related to a low basal level of activation of the clotting system in normal individuals.