Rabbit Aorta Research Articles

Increased receptor expression supports vascular reactivity of the rabbit aorta during preservation.

The mechanistic understanding of vascular functional impairment during preservation time helps determine the optimal time frame in which explanted arteries can be used. The method of choice is to measure vascular reactivity and receptor expression. Our goal was to study the influence of preservation for 24 and 48 h on vascular reactivity and receptor expression in rabbit aorta. Aortic rings preserved in Krebs-Henseleit solution were evaluated fresh (t0), 24 h (t24) and 48 h (t48) after harvest for (i) vascular reactivity as sensitivity (pD2) and maximum effect in response to potassium chloride, U46619 (thromboxane-A2 agonist), phenylephrine, carbachol and isoproterenol, in an organ bath; and for (ii) expression of α1, β2 and thromboxane-prostanoid receptors, by immunofluorescence. Compared to the control, after 24 h of preservation, potassium chloride-induced pD2 increased a significant 3.6%, whereas U46619-induced vasoconstriction decreased 9%. None of the agonists affected vasodilation. Intimal and medial α1 receptor expression increased 2.5-fold. After 48 h of preservation, α1 expression and vasoconstrictor responses remained similar to those after 24 h of preservation, but in vasodilation the carbachol-induced maximum effect decreased 30% whereas isoproterenol-induced pD2 increased 4% and the maximum effect increased 10%. TP and β2 expression in the intima and media increased 1.8- and 2.5-fold, respectively. Up to 48 h of preservation, the adrenergic pathway and its receptors support vasoconstriction and vasodilation, despite a significant deterioration in the prostanoid pathway.

Effect of cholesterol- and palm oil-enriched diets on rabbit aorta and aortic valve calcification

Atherosclerosis and calcific aortic valvular disease share a number of risk factors. Among them, hypercholesterolemia promotes atherosclerosis. However, whether a cholesterol-rich diet induces aortic valve calcification remains unclear. The effect of palm oil on vascular and valvular calcification is unknown. To study and compare the effects of cholesterol- and palm oil-enriched diets on aorta and aortic valve calcification in a rabbit model. New Zealand White rabbits were fed for 16 weeks with cholesterol- (0.3% cholesterol, n = 7) or palm oil-enriched diet (5% palm oil, n = 6) supplemented with vitamin D2 (25,000U/day/2.5 kg). Computed tomography (CT) was performed at regular intervals. Heart and aorta were collected for histological analyses. The cholesterol-rich diet provoked aortic atherosclerosis. It also induced a 2-fold increase of the aortic valve area compared to rabbits fed with a regular chow diet, with cell and lipid accumulation in the fibrosa. All rabbits displayed calcification of the aortic wall detectable in vivo by CT in 2 rabbits out of 7. Histology revealed calcification in the aortic valve of 4 rabbits out of 7 and thickening of valvular fibrosa. In contrast to the cholesterol-rich diet, the palm oil-rich diet did not lead to thickened aortic intima or aortic valve nor lipid accumulation. Interestingly, all rabbits treated with palm-oil enriched diet exhibited massive aortic wall calcification, characterized by the presence of large calcification nodules in the aortic media detectable in vivo by CT in 5 rabbits out of 6. Calcification was also found in the aortic valve fibrosa of 3 rabbits out of 6 and extracellular matrix remodeling was observed around the calcification nodules of the aortic media. Both diets induced histological changes and calcification of the aorta and aortic valve. However, the lesions differed between the two diets, suggesting different pathophysiological mechanisms.

Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits

BackgroundEffects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date.MethodsA group of rabbits received standard chow (SC) for 6 weeks (“negative control”; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified.ResultsAfter CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells.ConclusionsIn rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.

Undercarboxylated osteocalcin has no adverse effect on endothelial function in rabbit aorta or human vascular cells.

Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of ucOC on endothelial function in animal models ex vivo and human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand white rabbits and cell culture techniques were used on human aortic endothelial cells (HAECs) to assess the effect of ucOC in normal and high‐glucose environments. Overall, ucOC, both 10 and 30 ng/ml, did not significantly alter acetylcholine‐induced blood vessel relaxation in rabbits (p > .05). UcOC treatment did not cause any significant changes in the immunoreactivity of cellular signalling markers (p > .05). In HAEC, ucOC did not change any of the assessed outcomes (p > .05). UcOC has no negative effects on endothelial function which is important to reduce the risks of off target adverse effects if it will be used as a therapeutic option for metabolic disease in the future.

Estimating Arterial Cyclic Strain from the Spacing of Endothelial Nuclei

BackgroundThe non-uniform distribution of atherosclerosis within the arterial system is widely attributed to variation in haemodynamic wall shear stress. It may also depend on variation in pressure-induced stresses and strains within the arterial wall; these have been less widely investigated, at least in part because of a lack of suitable techniques.ObjectivesHere we show that local arterial strain can be determined from impressions left by endothelial cells on the surface of vascular corrosion casts made at different pressures, even though only one pressure can be examined in each vessel. The pattern of pits in the cast caused by protruding endothelial nuclei was subject to “retro-deformation” to identify the pattern that would have occurred in the absence of applied stresses.MethodsRetaining the nearest-neighbour pairs found under this condition, changes in nearest-neighbour vectors were calculated for the pattern seen in the cast, and the ratio of mean changes at different pressures determined. This approach removes errors in simple nearest-neighbour analyses caused by the nearest neighbour changing as deformation occurs.ResultsThe accuracy, precision and robustness of the approach were validated using simulations. The method was implemented using confocal microscopy of casts of the rabbit aorta made at systolic and diastolic pressures; results agreed well with the ratio of the macroscopic dimensions of the casts.ConclusionsApplying the new technique to areas around arterial branches could support or refute the hypothesis that the development of atherosclerosis is influenced by mural strain, and the method may be applicable to other tissues.

Intravascular Photoacoustic and Autofluorescence Imaging for Detecting Intraplaque Hemorrhage: A Feasibility Study

Intraplaque hemorrhage (IPH), which is a trigger and conveys all blood components into the plaque, influencing the cholesterol crystal formation and retention, haemoglobin and oxidative enzymes, and blood-borne proteolytic activity. IPH is one of the key determinants for plaque vulnerability. In this paper, we proposed a dual-modality endoscope probe with a diameter of 1 mm for simultaneously detecting the lipid core and IPH, our system was composed of photoacoustic imaging (PAI) and near-infrared auto-fluorescence imaging (NIRAFI). The lipid as endogenous marker of intravascular PAI could visualize the lipid distribution of atherosclerotic plaque, and bilirubin as the marker of intravascular NIRAFI was used to locate and quantify the IPH. The phantom and ex vivo rabbit aorta experiments had proved the feasibility and capability of the dual-mode probe for imaging IPH and lipid core expansion. And the results indicated that the dual-mode intravascular endoscope had the potential for accurately detecting IPH in atherosclerotic plaques.

A novel technique for laser-assisted revascularization: an in vitro pilot study.

The common limitation of surgical revascularization procedures for severe tissue ischemia due to cardiovascular diseases is the need to interrupt blood flow during the intervention. We aim to introduce a new technique that allows a sutureless, non-occlusive revascularization. A 3-step technique was developed using rabbit's aorta to simulate a side-to-side anastomosis model. It enables the creation of a bypass circuit for revascularization. The first step was the soldering of 2 vessels in a side-to-side fashion based on the laser-assisted vascular anastomosis (LAVA) principle using a diode laser emitting irradiation at 810 nm with an albumin-based solder patch between them, followed by the creation of a channel within the patch using either a holmium-doped yttrium aluminum garnet laser (Ho:YAG) at λ = 2100 nm or a xenon-chloride excimer laser (XeCl) at λ = 308 nm. Thereby, a bypass circuit was created, thus allowing a non-ischemic revascularization. The system was deemed functional when a flow was observed across the anastomosis. The highest average tensile strength recorded after side-to-side LAVA using a diode laser power of 3.2 W for 60 s was 2278.6 ± 800 mN (n = 20). The Ho:YAG laser created the channels with less tension on the anastomosis than the excimer laser. Histological analysis showed limited thermal damage and good patch-tissue adaptation. The preliminary results of this feasibility study outline the foundations for an entirely sutureless laser-assisted revascularization procedure. The next studies will evaluate the rheological parameters across the bypass circuit to optimize the post-anastomotic flow.

Аtherosclerosis-like changes in the rabbit aortic wall induced by immunization with native high-density lipoproteins.

IntroductionA high level of total cholesterol or low‐density lipoprotein (LDL) cholesterol is considered the main cause of atherosclerosis and cardiovascular disease. For this reason, experimental atherosclerosis is induced by creating high blood cholesterol in animals. However, the hypothesis that atherosclerotic processes are mostly caused by immune (autoimmune) mechanisms has recently been gaining traction. At the same time, no experimental model has been developed that clearly demonstrates the autoimmune mechanism by which atherosclerosis develops and reproduces the full picture of atherosclerosis solely by means of an immune response, without resorting to additional interventions such as a high‐cholesterol diet or the use of genetic models of hyperlipidemia. Previously, we were able to induce atherosclerosis‐like lesions in the aorta and the development of pericardial fat in rats by immunizing them with human native lipoproteins. The purpose of this study was to test whether atherosclerosis can be induced in normocholesterolaemic rabbits by immunizing them with human native high‐density lipoproteins (hnHDL).MethodsRabbits were immunized with hnHDL. Aortic wall structure, plasma cholesterol level, and antibodies against HDL were studied.ResultsImmunization with hnHDL was found to cause atherosclerosis‐like lesions in the rabbit aorta such as adipocytic and chondrocytic metaplasia, proteoglycan deposits, leukocytic infiltration. Atherosclerosis‐like lesions developed in the aorta of hnHDL‐immunized rabbits against a background of normal blood LDL‐cholesterol level. Therefore, a high plasma cholesterol level is not the sole cause of atherosclerosis. The immune response against HDL is an independent cause of atherogenesis.ConclusionsA rabbit model of atherosclerosis caused by immunization with hnHDL can be widely used to examine the mechanisms occurring during atherogenesis.

Empagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

A novel self-expanding primarily bioabsorbable braided flow-diverting stent for aneurysms: initial safety results

IntroductionThe advent of metal flow-diverting stents has provided neurointerventionalists with an option for treating aneurysms without requiring manipulations within the aneurysm sac. The large amount of metal in these stents,...

Ex vivo and in vivo studies of Viola tricolor Linn. as potential cardio protective and hypotensive agent: Inhibition of voltage-gated Ca++ ion channels.

Viola tricolor Linn. is used as cardio-protective and anti-hypertensive agent in traditional medicine. Current study objective was to evaluate cardio-protective and hypotensive effects of Viola tricolor L. in vitro and in vivo studies. Viola tricolor L. crude extract (Vt.Cr) and its fractions (Aqueous and organic) were tested at rabbit atria and aorta coupled to Power Lab Data Acquisition System for cardio depressant and vasorelaxant effects in vitro whereas in vivo Blood Pressure was checked by invasive method in normotensive ketamine-diazepam anesthetized rats. Isoproterenol was employed for acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) development and cardioprotective effects of Vt.Cr were evaluated hemodynamically and histopathologically. Vt.Cr and its fractions decreased heart rate and contractile force in paired atria and relaxed Phenylephrine (1µM) and K+ (80mM) stimulated contractions in aorta possibly mediated through Voltage dependent L-type calcium channels blockage supported by in vivo hypotensive action. In LVH, Vt.Cr lowered Angiotensin Converting Enzymes and renin, increased cyclic Guanosine Monophosphate and nitric oxide levels, decreased cardiomyocytes size and fibrosis attributed to Gallic acid as detected by High Performance Liquid Chromatography. Partial positive results were seen hemodynamically and histologically in AMI Viola tricolor L. showed vasorelaxant, cardio-relaxant, hypotensive, and cardio protective effect validating traditional practice in cardiovascular disorders.

Hypotensive, vaso-relaxant, cardio-depressant and diuretic effect of crude extract of <i>Crotalaria burhia</i> (Fabaceae)

Purpose: To examine 70 % aqueous-methanol crude extract of Crotalaria burhia (Cb.Cr) for its hypotensive and diuretic effects.
 Methods: The effect of intravenous administration of Cb.Cr on blood pressure (BP) of normotensive anesthetized rats was studied. In vitro experiments on rabbit isolated aortic and atrial preparations were performed to elucidate the mechanism of action. The diuretic effect was assessed following oral administration of Cb.Cr in rats.
 Results: Intravenous administration of Cb.Cr produced 14.70 ± 1.21, 22.00 ± 2.24 and 36.21 ± 2.65 % reduction in mean arterial blood pressure of the rats at doses of 1, 3 and 10 mg/kg, respectively. It was more potent in relaxing potassium (80 mM)- than phenylephrine (1 μM)-induced contractions in isolated aorta of rabbit with half-maximal effective concentration (EC50) values of 0.58 ± 0.03 and 1.58 ± 0.16 mg/mL, respectively, which are similar to verapamil. The extract showed depressant effects on spontaneously beating atrial preparations of rabbit in a dose-dependent manner. Moreover, Cb.Cr also increased urine volume and urinary electrolyte excretion in rats.
 Conclusion: Crotalaria burhia crude extract exhibits hypotensive and diuretic effects in rats. The hypotensive activity of the extract possibly involves vasodilator, cardio-depressant, calcium channel blocking and diuretic actions.
 Keywords: Khip, Crotalaria burhia, Calcium channel blocker, Antihypertensive, Diuretic

Influence of Ageing on Vascular Reactivity and Receptor Expression in Rabbit Aorta: A Complement to Elastocalcinosis and Smooth Muscle Mechanisms.

AimTo contribute to the knowledge about the mechanisms involved in aortic stiffness due to ageing.Materials and MethodsAortic rings from young (1.5±0.5 months, 0.8±0.2 kg), adult (6±0.5 months, 2.7±0.5 kg) and old (28±8 months, 3.2±0.8 kg) male New Zealand rabbits were used to evaluate: 1) intima-media thickness by optical microscopy; 2) vascular reactivity (VR) in terms of sensitivity (pD2) and efficacy (Emax) to KCl; phenylephrine (PE); U-46619, a thromboxane A2 receptor agonist, TXA2; carbachol (CCh), isoproterenol and sodium nitroprusside (SNP), using organ bath experiments; and 3) the expression of receptors α1, β2 and thromboxane-prostanoids (TP), by immunofluorescence.ResultsAgeing 1) did not change the thickness of tunica; 2) significantly reduced the pD2 to KCl, increased the pD2 to PE and reduced both the pD2 and Emax to TXA2, CCh and isoproterenol, and reduced the pD2 to SNP; and 3) significantly increased the expression of α1 and β2 receptors in the intima and adventitia, and the expression of TP only in the adventitia.ConclusionOur results suggest that ageing makes the aorta more reactive to α1 adrenergic contraction, and it could be a compensation for lower responsiveness to prostanoids. The aged aorta is less reactive to endothelium-dependent and non-dependent relaxation, and the vessel seems to try to compensate for that stiffness increasing β2 receptors, although probably less functional. These results complement the proposed mechanisms of elastocalcinosis and smooth muscle rigidity, expanding the vision that should guide the treatment of aortic stiffness due to aging.

Alterations in Copper Homeostasis in Rabbit Model of Atherosclerosis

Copper concentrations decrease in atherosclerotic tissues. The present study was undertaken to determine overall alterations in copper homeostasis in the pathogenesis of atherosclerosis. New Zealand white rabbits, aged 10‐weeks‐old, were fed a rodent chow diet containing 1% (w/w) cholesterol or the same diet without cholesterol as control. Twelve weeks after respective diet feeding, the animals were euthanatized by sodium pentobarbital. Rabbits fed cholesterol‐containing diet developed hyperlipemic as defined by a significant increase in the total plasma cholesterol and atherosclerotic lesions in aorta. Copper concentrations in the atherosclerotic tissues were significantly decreased while serum copper concentrations were increased in the hyperlipemic animals in comparison with controls. A detailed analysis revealed that copper concentration in abdominal aorta of the hyperlipemic rabbits was negatively correlated with the severity of the atherosclerotic lesion, stenosis of the lumen area, and collagen deposition. In addition, copper concentrations in the kidney of hyperlipemic rabbits were increased, but in the heart, liver, spleen and lung were decreased. These results suggest that in the pathogenesis of atherosclerosis, changes in copper homeostasis are not only observable in the atherosclerotic tissues, but also in multiple organ systems. These changes would be additive to atherosclerosis as a high risk of cardiovascular disease in humans.Support or Funding InformationWest China Hospital, Sichuan University(A) The percentage of the aortae staining positively for lipid(Longitudinal of suprarenal abdominal aortae was stained with oil red O). Sections of infrarenal abdominal aortae were stained with EVG for microscopic quantification of lesion areas, (B) the atherosclerotic lesion area and (C) the percent of stenosis of lumen area. Collagen fibers in the lesions were assessed by picrosirius red staining, the percent of Collagen in lesion area. (*P < 0.05)Figure 1The concentration of copper in tissues and plasma.(A) cardiac copper concentration; (B) liver copper concentration; (C) spleen copper concentration; (D) lung copper concentration; (E) kidney copper concentration; (F) duodenum copper concentration; (G) abdominal aortic copper; (H) plasma copper concentration. (*P < 0.05)Figure 2

Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue

High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30–60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.

Matching Static and Dynamic Compliance of Small‐Diameter Arteries, with Poly(lactide‐co‐caprolactone) Copolymers: In Vitro and In Vivo Studies

Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter vascular graft failure. To minimize this mismatch, several poly-l-lactide-co-ε-caprolactone (PLC) copolymers are evaluated as candidate materials to fabricate a small diameter graft. Using these materials, tubular prostheses of 4 mm inner diameter are fabricated by dip-coating. In vitro static and dynamic compliance tests are conducted, using custom-built apparatus featuring a closed flow system with water at 37 °C. Grafts of PLC monomer ratio of 50:50 are the most compliant (1.56% ± 0.31∙mm Hg-2 ), close to that of porcine aortic branch arteries (1.56% ± 0.43∙mm Hg-2 ), but underwent high continuous dilatation (87 µm min-1 ). Better matching is achieved by optimizing the thickness of a tubular conduit made from 70:30 PLC grafts. In vivo implantation and function of a PLC 70:30 conduit of 150 µm wall-thickness (WT) are tested as a rabbit aorta bypass. An implanted 150 µm WT PLC 70:30 prosthesis is observed over 3 h. The recorded angiogram shows continuous blood flow, no aneurysmal dilatation, leaks, or acute thrombosis during the in vivo test, indicating the potential for clinical applications.

Immunization with the Gly1127-Cys1140 amino acid sequence of the LRP1 receptor reduces atherosclerosis in rabbits. Molecular, immunohistochemical and nuclear imaging studies.

Background: The LRP1 (CR9) domain and, in particular, the sequence Gly1127-Cys1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis.Methods: Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hMΦ) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells.Results: P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hMΦ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hMΦ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUVmean) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group.Conclusions: P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature.

The Role of Angiotensin II Type 1 Receptor-Activating Antibodies in Vascular Inflammation

Background: Studies demonstrated the autoantiboies against angiotension II type 1 receptor (AT1-AAs) could induce vascular endothelial dysfunction. Our objective is to investigate the effect of AT1-AAs on atherosclerosis. Methods: AT1-AAs were purified from sera of patients with primary hypertension. Thirty-six New Zealand white rabbits were underwent balloon-induced abdominal aortic endothelial injury and fed an atherogenic diet for 6 weeks and were randomly divided into six groups with different drugs for 4 weeks. The levels of AT1-AAs, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in different stage were detected by ELISA. The abdominal aortas of rabbits were stained with hematoxylin and eosin. The expression of matrix metalloproteinases-2 (MMP-2) in aortic tissue was detected by Western blotting. Results: The levels of TNF-α in the eighth week (0.17 ± 0.04, 0.34 ± 0.08) and in the tenth week (0.23 ± 0.04, 0.54 ± 0.11) were significantly higher than that at the beginning of test (0.04 ± 0.03, 0.08 ± 0.02) in the group of AT1-AAs with low-dose and high-dose (P < 0.05). The level of IL-6 stimulated by high dose AT1-AAs was higher in the tenth week (0.42 ± 0.08) than that at the beginning of test (0.04 ± 0.01, P < 0.05). The relative area of plaque was significantly (P < 0.05) increased in group of AT1-AAs with low-dose (46.99% ± 13.06%) and high-dose (66.11% ± 19.67%) compared with other groups. The expression of MMP-2 was significantly higher (P < 0.05) in group AT1-AAs with low dose (0.42 ± 0.03) and high dose (0.54 ± 0.04) than that in other groups. Conclusion: The results showed that the AT1-AAs could aggravate the inflammatory reaction and the plaque formation.

Filament inadequate wall apposition of the different ends of flow diverters in the abdominal aorta of rabbits.

Flow diverters (FDs) with flared ends (FEs) or straight ends (SEs) are used either alone or when overlapped to treat complex intracranial aneurysms. We evaluated filament inadequate wall apposition (IWA) of the FEs and SEs of FDs invivo. A total of 24 FDs with FEs and SEs were placed in an overlapping manner in the abdominal aortae of six rabbits (two sets per rabbit). Digital subtraction angiography was performed immediately after stent insertion and three months later. The anatomical and histopathological aortic features at FEs and SEs were evaluated. Angiography revealed no significant difference in terms of changes in arterial diameter between the FE and SE groups (p = 0.877). Gross anatomical evaluation revealed IWA of the different ends of FDs but no thrombi or bleeding, showing that the metallic filaments were not in touch with the vessel wall and nor had they penetrated the vessel wall. The filaments' IWA rates of FEs and SEs were 8.33% and 8.85%, respectively. The IWA rate at overlapping ends was lower than that at non-overlapping ends. The maximum neo-intimal thickness at FEs was greater than that at SEs (149.4 ± 48.9 and 98.6 ± 26.6 µm, respectively; p < 0.001). Both the FEs and SEs of FDs can exhibit IMA. IWA events are reduced at the overlapped regions. On pathological evaluation, FEs increased neo-intimal thicknesses more than SEs did, but hyperplasia was minimal on angiography.

Endothelium resolving simulations of wall shear-stress dependent mass transfer of LDL in diseased coronary arteries

In the present study, we investigate blood flow and mass transfer of the low-density lipoprotein (LDL) in a simplified axisymmetric geometry with a mathematically well-defined narrowing (stenosis), which mimics a diseased human coronary artery. The interior of the arterial wall is represented as a porous media containing multi-layered structures of different thickness. This multi-layered structure includes anatomically realistic sublayers: endothelium, intima, internal elastic layer (IEL), media and adventitia. The coupling between the blood flow and mass transfer of LDL in the lumen (interior of artery) and arterial wall is established through a multipore model at the lumen/endothelium interface. This multipore model takes into consideration three different contributions for transport of LDL: normal and leaky junctions of endothelial cells, as well as their vesicular pathway. A comprehensive mathematical model, which is based on solving the set of PDEs for conservation of mass, momentum, and concentration, is completed by introducing the wall shear-stress (WSS) dependent transport properties of the arterial wall. Several variants of the model are evaluated, including the constant and wall shear-stress dependent transport properties of the endothelium, as well as different representation of the arterial wall internal structure. The response of the model on changing the transmural pressure (to simulate hypertension effects) and geometrical shapes of the stenosis (to mimic the various stages of atherosclerosis development) is also presented. It is shown that the present model can predict the levels of LDL inside the arterial wall in good agreement with experimental studies in pressurized rabbit aorta under similar conditions. The model is recommended for future simulations of LDL accumulation in the patient-specific cardiovascular system conditions.