Muscular Arteries Research Articles

Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome.

Clinical trials have demonstrated that lonafarnib, a farnesyltransferase inhibitor, extends the lifespan in patients afflicted by Hutchinson-Gilford progeria syndrome, a devastating condition that accelerates many characteristics of aging and results in premature death due to cardiovascular sequelae. The US Food and Drug Administration approved Zokinvy (lonafarnib) in November 2020 for treating these patients, yet a detailed examination of drug-associated effects on cardiovascular structure, properties, and function has remained wanting. In this paper, we report encouraging outcomes of daily post-weaning treatment with lonafarnib on the composition and biomechanical phenotype of elastic and muscular arteries as well as associated cardiac function in a well-accepted mouse model of progeria that exhibits severe perimorbid cardiovascular disease. Lonafarnib resulted in 100% survival of the treated progeria mice to the study end-point (time of 50% survival of untreated mice), with associated improvements in arterial structure and function working together to significantly reduce pulse wave velocity and improve left ventricular diastolic function. By contrast, neither treatment with the mTOR inhibitor rapamycin alone nor dual treatment with lonafarnib plus rapamycin improved outcomes over that achieved with lonafarnib monotherapy.

Establishment of a canine model of pulmonary arterial hypertension induced by dehydromonocrotaline and ultrasonographic study of right ventricular remodeling

ABSTRACT Objective Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling. Methods Twenty healthy beagle dogs (8–10 kg) were randomly divided into control group (N-dimethylformamide, n = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed. Results At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP (r = 0.74, P < .001), mRVP (r = 0.72, P < .001), PASP (r = 0.75, P < .001), mPAP (r = 0.72, P < .001) and PVR (r = 0.68, P < .001). There was a significant positive correlation between RVLS and RVHI (r = 0.74, P < .001). Conclusion The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH.

Chemo-mechanical modeling of smooth muscle cell activation for the simulation of arterial walls under changing blood pressure

In this paper, a novel chemo-mechanical model is proposed for the description of the stretch-dependent chemical processes known as Bayliss effect and their impact on the active contraction in vascular smooth muscle. These processes are responsible for the adaptive reaction of arterial walls to changing blood pressure by which the blood vessels actively support the heart in providing sufficient blood supply for varying demands in the supplied tissues. The model is designed to describe two different stretch-dependent mechanisms observed in smooth muscle cells (SMCs): a calcium-dependent and a calcium-independent contraction. For the first one, stretch of the SMCs leads to an inlet of calcium ions which activates the myosin light chain kinase (MLCK). The increased activity of MLCK triggers the contractile units of the cells resulting in the contraction on a comparatively short time scale. For the calcium-independent contraction mechanism, stretch-dependent receptors of the cell membrane stimulate an intracellular reaction leading to an inhibition of the antagonist of MLCK, the myosin light chain phosphatase resulting in a contraction on a comparatively long time scale. An algorithmic framework for the implementation of the model in finite element programs is derived. Based thereon, it is shown that the proposed approach agrees well with experimental data. Furthermore, the individual aspects of the model are analyzed in numerical simulations of idealized arteries subject to internal pressure waves with changing intensities. The simulations show that the proposed model is able to describe the experimentally observed contraction of the artery as a reaction to increased internal pressure, which can be considered a crucial aspect of the regulatory mechanism of muscular arteries.

Fibromuscular Dysplasia – Underrecognized Vasculopathy with Female Preponderance

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease with strong female preponderance. However the diagnosis of the disease is low. FMD affects medium-sized muscular arteries, predominantly renal arteries, but equally carotid and vertebral arteries. It leads to artery stenosis, occlusion, aneurysm or dissection. The clinical picture depends on the affected blood vessels. It is most commonly recognized as a cause of hypertension in young female patients. In the case of involvement of cranial and cervical arteries, the clinical picture is mostly nonspecific, with headache, migraine and tinnitus. In registries, females had more frequent classical symptoms of cerebrovascular FMD like pulsatile tinnitus, cervical bruit and neck pain, and males have more frequently visceral affection (abdominal pain, renal impairment and renal infarction). Also, man had more frequently more sever clinical presentation like arterial dissection or arterial aneurysm. At the age of diagnosis males are younger compared to females. Large cohort studies showed the association of FMD with female sex, migraine, and intracranial aneurysm. FMD is an under-recognized vascular disease, more prevalent in females, but exhibiting more sever clinical presentation in males.

A Proteomic Screen to Unravel the Molecular Pathways Associated with Warfarin-Induced or TNAP-Inhibited Arterial Calcification in Rats

Arterial media calcification refers to the pathological deposition of calcium phosphate crystals in the arterial wall. This pathology is a common and life-threatening complication in chronic kidney disease, diabetes and osteoporosis patients. Recently, we reported that the use of a TNAP inhibitor, SBI-425, attenuated arterial media calcification in a warfarin rat model. Employing a high-dimensionality unbiased proteomic approach, we also investigated the molecular signaling events associated with blocking arterial calcification through SBI-425 dosing. The remedial actions of SBI-425 were strongly associated with (i) a significant downregulation of inflammatory (acute phase response signaling) and steroid/glucose nuclear receptor signaling (LXR/RXR signaling) pathways and (ii) an upregulation of mitochondrial metabolic pathways (TCA cycle II and Fatty Acid β-oxidation I). Interestingly, we previously demonstrated that uremic toxin-induced arterial calcification contributes to the activation of the acute phase response signaling pathway. Therefore, both studies suggest a strong link between acute phase response signaling and arterial calcification across different conditions. The identification of therapeutic targets in these molecular signaling pathways may pave the way to novel therapies against the development of arterial media calcification.

A new mouse model of elastin haploinsufficiency highlights the importance of elastin to vascular development and blood pressure regulation

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (Eln+/−) was generated that recapitulates many aspects of the human disease, including increased medial SMC layers and elastic lamellae, large artery stiffness, and hypertension. The vascular changes in these mice were thought to be responsible for the hypertension phenotype. However, a renin gene (Ren) duplication in the original 129/Sv genetic background and carried through numerous strain backcrosses raised the possibility of renin-mediated effects on blood pressure. To exclude excess renin activity as a disease modifier, we utilized the Cre-LoxP system to rederive Eln hemizygous mice on a pure C57BL/6 background (Sox2-Cre;Elnf/f). Here we show that Sox2-Cre;Eln+/f mice, with a single Ren1 gene and normal renin levels, phenocopy the original global knockout line. Characteristic traits include an increased number of elastic lamellae and SMC layers, stiff elastic arteries, and systolic hypertension with widened pulse pressure. Importantly, small resistance arteries of Sox2-Cre;Eln+/f mice exhibit a significant change in endothelial cell function and hypercontractility to angiotensin II, findings that point to pathway-specific alterations in resistance arteries that contribute to the hypertensive phenotype. These data confirm that the cardiovascular changes, particularly systolic hypertension, seen in Eln+/− mice are due to Eln hemizygosity rather than Ren duplication.

Concentration of non-myocyte proteins in arterial media of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

The most common inherited cause of vascular dementia and stroke, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is caused by mutations in NOTCH3. Post-translationally altered NOTCH3 accumulates in the vascular media of CADASIL arteries in areas of the vessels that exhibit profound cellular degeneration. The identification of molecules that concentrate in the same location as pathological NOTCH3 may shed light on processes that drive cytopathology in CADASIL. We performed a two phase immunohistochemical screen of markers identified in the Human Protein Atlas to identify new proteins that accumulate in the vascular media in a pattern similar to pathological NOTCH3. In phase one, none of 16 smooth muscle cell (SMC) localized antigens exhibited NOTCH3-like patterns of expression; however, several exhibited disease-dependent patterns of expression, with antibodies directed against FAM124A, GZMM, MTFR1, and ST6GAL demonstrating higher expression in controls than CADASIL. In contrast, in phase two of the study that included 56 non-SMC markers, two proteins, CD63 and CTSH, localized to the same regions as pathological NOTCH3, which was verified by VesSeg, a customized algorithm that assigns relative location of antigens within the layers of the vessel. Proximity ligation assays support complex formation between NOTCH3 fragments and CD63 in degenerating CADASIL media. Interestingly, in normal mouse brain, the two novel CADASIL markers, CD63 and CTSH, are expressed in non-SMC vascular cells. The identification of new proteins that concentrate in CADASIL vascular media demonstrates the utility of querying publicly available protein databases in specific neurological diseases and uncovers unexpected, non-SMC origins of pathological antigens in small vessel disease.

Serum OPG and RANKL Levels as Risk Factors for the Development of Cardiovascular Calcifications in End-Stage Renal Disease Patients in Hemodialysis

Cardiovascular calcifications (CVC) are frequently observed in chronic kidney disease (CKD) patients and contribute to their cardiovascular mortality. The aim of the present study was to investigate the impact of osteoprotegerin (OPG)/Receptor Activator of NF-κΒ (RANK)/RANK ligand (RANKL) pathway in the development and evolution of CVCs in hemodialysis patients. In total, 80 hemodialysis patients were assessed for the presence of vascular (abdominal aorta and muscular arteries) calcifications and results were correlated to serum OPG and RANKL levels and the OPG/RANKL ratio. Traditional cardiovascular risk factors and mineral bone disease parameters were also estimated. The presence of VCs was also evaluated 5 years after the initiation of the study, and results were correlated to the initial serum OPG levels. Age, diabetes mellitus, coronary artery disease and OPG levels (p < 0.001) were associated with VCs, whereas RANKL levels were not. Multivariate analysis though revealed that only OPG levels were significantly associated with abdominal aorta calcifications (p = 0.026), but they were not correlated with the progression of VCs. Serum OPG levels are positively and independently associated with VCs in HD patients, but not with their progression. RANKL levels did not show any associations, whereas further studies are needed to establish the significance of OPG/RANKL ratio.

Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.

Mutations in BMPR2 (bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH. SMC-specific Bmpr2-/- mice (BKOSMC) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from BKOSMC mice, human PASMC with BMPR2 reduced by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation were compared to controls, to investigate the phenotype and underlying mechanism. BKOSMC mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (β-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (β-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension. Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH.

Increased arterial pressure volume index and cardiovascular risk score in China

Background and objectiveThe new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR).MethodsAccording to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5–9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline.ResultsThe study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units.ConclusionAPI, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.

The Age–Stiffness Relationships of Elastic and Muscular Arteries in a Control Population and in End-Stage Renal Disease Patients

Arterial dysfunction is major risk factor for cardiovascular complications, and arterial stiffness is an independent risk factor in end-stage renal disease patients. As the distance from the heart increases, arterial stiffness (pulse wave velocity) becomes progressively more marked. This generates a centrifugal stiffness gradient, which leads to partial, continuous local wave reflections, which in turn attenuate the transmission of pulsatile pressure into the microcirculation, thus limiting the potentially deleterious outcomes both upstream (on the heart: left-ventricular hypertrophy and coronary perfusion) and downstream (on the renal and cerebral microcirculation: reduced glomerular filtration and impaired cognitive functions). The impact of arterial aging is greater on the aorta and central capacitive arteries, and it is characterized by a loss or reversal of the physiological stiffness gradient between central and peripheral arteries. Recently, however, in contrast to observations on the aorta, several studies have shown less pronounced, absent, or even negative associations between muscular peripheral arteries and age–stiffness relationships, which may be associated with a decrease in or reversal of the stiffness gradient. These findings point to a potential benefit of assessing the muscular peripheral arteries to predict the risk of cardiovascular disease and suggest that reversal of the stiffness gradient may be an independent risk factor for all-cause mortality.

The lymphatic drainage systems in the brain: a novel target for ischemic stroke?

Recent studies have proposed three lymphatic drainage systems in the brain, that is, the glymphatic system, the intramural periarterial drainage pathway, and meningeal lymphatic vessels, whose roles in various neurological diseases have been widely explored. The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid. The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media. Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses. After ischemic stroke, impairment of these systems could lead to cerebral edema, accumulation of toxic factors, and activation of neuroinflammation, while restoration of their normal functions can improve neurological outcomes. In this review, we summarize the basic concepts of these drainage systems, including drainage routes, physiological functions, regulatory mechanisms, and detection technologies. We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke, as well as recent advances in therapeutic strategies targeting these drainage systems. These findings provide information for potential novel strategies for treatment of stroke.

Effects of atorvastatin in suppressing pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease

ObjectiveTo investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. MethodsEighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). ResultsCompared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p < 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p < 0.05). ConclusionThe present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.

Invasive validation of the Antares algorithm for determining central blood pressure based on upper arm oscillometric pulse waves in patients with type 2 diabetes

IntroductionAntares is a pulse wave analysis (PWA) algorithm designed to allow a non-invasive estimation of central (aortic) blood pressure (cBP) using automated oscillometric blood pressure (BP) devices. Diabetes may affect...

PS-BPC02-7: RADIAL-DIGITAL PULSE WAVE VELOCITY: STIFFNESS OF SMALL CONDUIT ARTERIES INCREASES AFTER NITROGLYCERIN ADMINISTRATION

Objective: The alteration of the physiological stiffness gradient within larger vessels would increase the transmission of greater pulsatility to the microcirculation, thus explaining the damage to the pressure-sensitive organs. We aimed to describe the response of small conduit arteries of the hand (radial-digital PWV, rd-PWV) following the pharmacological alteration of the stiffness gradient using nitroglycerin. Design and method: Simultaneous application of piezoelectric sensors (Complior) at the level of the carotid (c), the radial artery (r) and the tip of the index finger (d) was used to calculate the rd-PWV by the following formula (rd-PWV = cd-cr direct distances/cd-cr transit times). Rd-PWV was obtained before and 4 minutes after a sublingual administration of 0.4 mg of NTG, in healthy adults (controls, n = 36) and patients with moderate chronic kidney disease (CKD, n = 30). Changes in arterial stiffness pre-post NTG and comparisons between the two groups were analyzed respectively with paired or independent samples t-tests. Results: Compared to controls, the CKD group was older (69 ± 15 years vs. 41 ± 20 years) and more hypertensive. Despite similar cd-PWV and cr-PWV, rd-PWV was significantly lower in CKD than in controls (3.6 ± 1.4 m/s vs. 4.5 ± 1.8 m/s, p = 0.024), but this difference faded (p = 0.145) after adjustment for age. Post NTG, brachial blood pressure decreased and heart rate increased similarly between groups (see Table 1). Cr-PWV decreased after NTG (both groups p &lt; 0.001) while rd-PWV increased in controls (from 4.62 ± 1.49 m/s to 5.94 ± 2.29 m/s, p &lt; 0.001) and in CKD (from 3.71 ± 1.60 m/s to 5.18 ± 2.12 m/s, p &lt; 0.001), in a similar extent (p = 0.111 for interaction term). Cd-PWV significantly increased post-NTG only in the CKD group (p = 0.009). Conclusions: Again, we observed opposing changes in the regional stiffnesses of two distinct vascular territories following the administration of a vasodilator. Here, the two segments were mid-size and small conduit muscular arteries. This technique, adapted by our team for short peripheral arterial segments, may broaden our understanding of the consequences of the inversion of the stiffness gradient.

High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease.

Although macrophage infiltration has been proven to increase calcified artery media in chronic kidney disease (CKD) patients, the mechanism by which macrophages are involved in vascular calcification (VC) progression remains unclear. Taking advantage of miRNA-seq, RNA-seq, dual-luciferase reporter assay, qRT-PCR, and arteries from CKD patients as well as CKD mouse models, we identified that high-phosphate-stimulated macrophage-derived exosomes (Mexo-P) suppressed let-7b-5p expression in VSMCs, which further upregulated TGFBR1. Moreover, gain-and-loss-of-function assays were used to determine the regulatory effects and downstream mechanism of let-7b-5p and TGFBR1 on VC. Mechanically, Mexo-P induced VSMC TGFBR1 upregulation by suppressing let-7b-5p, which further amplifies SMAD3/RUNX2 signaling and thereby contributes to VC. Our findings indicate that macrophage-derived exosomes promote CKD-associated VC through the let-7b-5p/TGFBR1 axis in high-phosphate conditions. Our study provides insight into macrophages associated with VC, which might be potential therapeutical targets for VC.

Histopathological and Haematological Changes Observed in Adult Wistar Rats Administered with Momordica charantia (Bitter Melon) Aqueous Leaf Extract

This research work was carried out to investigate the effect of the aqueous leaf extract of Momordica charantia on some hematological parameters and ovaries of adult Wistar rats. Twenty five adult Wistar rats were grouped in to five (Control and A,B,C,D) and fed with saline, 100 mg/kg, 200 mg/kg, 400 mg/kg and 800 mg/kg of aqueous leaf extract of the plant respectively for 30 days. Blood was collected for packed cell volume, PCV, white blood cell count, WBC, red blood cell count, RBC and platelet count while ovaries were harvested for histopathological studies. This study was carried out at the Department of Medical Laboratory Science, Universityy of Benin, Edo State, Nigeria between October and December 2020. The results of the work showed that there was significant decrease in packed cell volume (PCV), and red blood cell count (RBC) compared with the control (p&lt;0.05) while dilation of blood vessels and thickening of tunica media of arteries were observed in ovaries of the rats. It was concluded that aqueous leaf extract of Momordica charantia has haematological and histomorphological effects on adult Wistar rats which could lead to anaemia and likely infertility.

Lupus Anticoagulant and Anticardiolipin Antibody IgG are Associated with Increased Atherosclerosis at the Suprainguinal Elastic and Infrainguinal Muscular Arteries in the Abdomen and Lower Extremities

PurposeWhether antiphospholipid antibodies (aPLs) cause atherosclerosis in certain arteries with specific compositions and locations remains unknown. We investigated the relationship between aPLs and their association with locations of atherosclerosis in the arteries of the abdomen and lower extremities.MethodsOf 2273 patients, 697 who underwent computed tomography angiography of the abdomen and lower extremities and aPL evaluation were included. Atherosclerosis distribution score (ADS) was employed to quantify atherosclerosis severity. Multiple linear regression analysis was performed using the ADS of the suprainguinal elastic and infrainguinal muscular arteries as dependent variables and all aPLs, conventional risk factors of atherosclerosis, and coagulation-related factors as independent variables.ResultsIn the suprainguinal elastic and infrainguinal muscular arteries, common risk factors for higher ADS were age, smoking, hypertension, higher glycated hemoglobin, male sex, decreased protein S, and increased homocysteine. Lupus anticoagulant (LA) and increased triglyceride level in the suprainguinal elastic arteries and anticardiolipin antibody (aCL) immunoglobulin (Ig)G, longer alcohol consumption duration, and increased fibrinogen level in the infrainguinal muscular arteries were also risk factors for higher ADS.ConclusionLA and aCL IgG were associated with atherosclerosis in the suprainguinal elastic and infrainguinal muscular arteries, respectively. aPLs could predict the location of atherosclerosis.

Polymyalgia rheumatica presenting as sternoclavicular arthritis: a case report

BackgroundPolymyalgia rheumatica and giant cell arteritis are systemic inflammatory conditions of the elderly. Polymyalgia rheumatica classically presents as a bilateral proximal muscle pain and stiffness syndrome. Biceps tenosynovitis is the commonest pathology in polymyalgia rheumatica. However according to literature, erosive sternoclavicular arthritis is a rare association of polymyalgia rheumatica. Giant cell arteritis is an inflammatory granulomatous arteritis predominantly involving large cerebral arteries. Thus, its classic clinical presentation includes severe headache with scalp tenderness, jaw claudication, and sudden painless loss of vision. Urological manifestations (prostatic vasculitis and epididymo-orchitis) were seldom reported in giant cell arteritis.Case presentationA 53-year-old Sinhalese man presented with progressive right-sided shoulder joint pain and neck pain associated with constitutional symptoms and episodic generalized headache. Examination revealed restricted movements of the right shoulder joint with nontender pulsatile bilateral temporal arteries. Blood testing showed elevated erythrocyte sedimentation rate and C-reactive protein. Color Doppler ultrasound of the superficial temporal artery revealed “halo sign.” The temporal artery showed infiltration of mononuclear cells in the arterial media and adventitia. Computed tomography revealed right sternoclavicular arthritis with incidental finding of ureteric stricture. The patient was treated with high-dose oral prednisolone, and good clinical and biochemical response was observed during follow-up.ConclusionPolymyalgia rheumatica–giant cell arteritis may rarely present as erosive sternoclavicular arthritis as the initial manifestation, mimicking many rheumatological conditions. Urological involvement such as ureteric strictures may be rare associations of primary systemic vasculitis. A high degree of suspicion combined with targeted investigations would allow early identification the polymyalgia rheumatica–giant cell arteritis syndrome in the presence of atypical manifestations, leading to improved patient outcomes.

Deletion of the P2Y2 receptor aggravates internal elastic lamina calcification in chronic kidney disease mice through upregulation of alkaline phosphatase and lipocalin-2.

Calcification of the medial layer, inducing arterial stiffness, contributes significantly to cardiovascular mortality in patients with chronic kidney disease (CKD). Extracellular nucleotides block the mineralization of arteries by binding to purinergic receptors including the P2Y2 receptor. This study investigates whether deletion of the P2Y2 receptor influences the development of arterial media calcification in CKD mice. Animals were divided into: (i) wild type mice with normal renal function (control diet) (n= 8), (ii) P2Y2 R-/- mice with normal renal function (n= 8), (iii) wild type mice with CKD (n= 27), and (iv) P2Y2 R-/- mice with CKD (n= 22). To induce CKD, animals received an alternating (0.2-0.3%) adenine diet for 7 weeks. All CKD groups developed a similar degree of chronic renal failure as reflected by high serum creatinine and phosphorus levels. Also, the presence of CKD induced calcification in the heart and medial layer of the aortic wall. However, deletion of the P2Y2 receptor makes CKD mice more susceptible to the development of calcification in the heart and aorta (aortic calcium scores (median ± IQR), CKD-wild type: 0.34 ± 4.3mg calcium/g wet tissue and CKD-P2Y2 R-/- : 4.0± 13.2mg calcium/g wet tissue). As indicated by serum and aortic mRNA markers, this P2Y2 R-/- mediated increase in CKD-related arterial media calcification was associated with an elevation of calcification stimulators, including alkaline phosphatase and inflammatory molecules interleukin-6 and lipocalin 2. The P2Y2 receptor should be considered as an interesting therapeutic target for tackling CKD-related arterial media calcification.