Wall Calcification Research Articles

MFG-E8 promotes osteogenic transdifferentiation of smooth muscle cells and vascular calcification by regulating TGF-\u03b21 signaling

Vascular calcification occurs in arterial aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Transforming growth factor-β1 (TGF-β1) is a key modulator driving the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), leading to vascular calcification. We hypothesize that milk fat globule–epidermal growth factor 8 (MFG-E8), a glycoprotein expressed in VSMCs, promotes the osteogenic transdifferentiation of VSMCs through the activation of TGF-β1-mediated signaling. We observe that the genetic deletion of MFG-E8 prevents calcium chloride-induced vascular calcification in common carotid arteries (CCAs). The exogenous application of MFG-E8 to aged CCAs promotes arterial wall calcification. MFG-E8-deficient cultured VSMCs exhibit decreased biomineralization and phenotypic transformation to osteoblast-like cells in response to osteogenic medium. MFG-E8 promotes β1 integrin–dependent MMP2 expression, causing TGF-β1 activation and subsequent VSMC osteogenic transdifferentiation and biomineralization. Thus, the established molecular link between MFG-E8 and vascular calcification suggests that MFG-E8 can be therapeutically targeted to mitigate vascular calcification.

Vascular calcification and fibroblast growth factor in resistant hypertension

Background . Pathological vascular calcification in hypertension (HTN) is studied worldwide. The relationship between endothelial dysfunction (ED) and vascular wall calcification in HTN has been demonstrated, and an increase in the level of fibroblast growth factor (FGF23) is considered one of the contributing factors. The aim of the study was to assess the incidence and severity of thoracic aortic calcification, and its relationship with fibroblast growth factor and ED in patients with resistant HTN. Design and methods . Ninety-two patients with resistant HTN were included. All of them underwent: 24-hour blood pressure monitoring (ABPM), the assessment ofendothelial function, the thoracic aortic calcium (TAC) index using multispiral computed tomography, and the level of FGF23. Results . According to the results of ABPM, patients were divided into group 1 with controlled HTN (n = 44) and group 2 with uncontrolled (n = 48) resistant HTN. In the 2nd group, there was an increase in TAC and ED, in both groups, changes in the blood flow velocity were recorded. There were no significant differences in FGF23 levels between the groups. We found a positive relationship between TAC and pulse pressure according to the results of ABPM (r = 0,49, p = 0,007), HTN duration (r = 0,68, p = 0,04) and a negative relationship with the duration of regular antihypertensive therapy (r = –0,33, p = 0,02). In addition, participants with higher FGF23 levels were older (r = 0,663, p = 0,006) and had a longer history of HTN (r = 0,57, p = 0,03). Conclusions . In patients with resistant HTN, ED and calcification of the thoracic aorta are more pronounced when the target blood pressure level is not achieved. The level of FGF23 is associated with an increase in the resistance indices assessed by dopplerography of the brachial artery and the severity of calcification of the thoracic aorta.

Transcavernosal transmekkel access in surgery of hard-to-reach basilar artery aneurysms

The manuscript provides clinical and anatomical rationale for interventions on hard-to-reach skull base aneurysms from transcavernosal access. The impact of basal surgery improved the capabilities of the accesses used in vascular neurosurgery, provided an overview of the hard-to-reach segment of the ACBM and the quality of aneurysm clipping. The low location of the BA apex, fetal type of structure, short size of the VAS and anatomical characteristics of the aneurysm (AA with dome direction to intercostal fossa, calcified AA walls, aneurysm with wide neck) complicate the use of pterional access. For anterolateral accesses the problem of surgical target view from the selected interspace, one of the boundaries of which is the ACA (optico-carotid, carotid-oculomotor interspace) remains. The problem of temporal lobe traction damage during surgical intervention has not been solved for lateral accesses. The proposed variant of trans-mechanteric transcavernosal access with resection of lateral parts of the upper scape, the apex of the temporal bone pyramid and destruction of the Dorello channel in the area of the described "postero-medial triangle of the skull base" opens the scape I zone and allows basal approach to the BA trunk and apex, especially at its low location.

1-Year Outcomes of Fluoropolymer-Based Drug-Eluting Stent in Femoropopliteal Practice: Predictors of Restenosis and Aneurysmal Degeneration.

This study aimed to investigate the 1-year risk of restenosis and aneurysmal degeneration and explore the associated factors after femoropopliteal implantation of fluoropolymer-based drug-eluting stents (FP-DESs) for symptomatic atherosclerotic peripheral artery disease in real-world practice. Although clinical trials have demonstrated that FP-DES implantation has favorable 1-year outcomes, its performance in real-world practice has not been well elucidated. This multicenter, prospective, observational study evaluated 1,204 limbs (chronic limb-threatening ischemia: 34.8%, mean lesion length: 18.6 ± 9.9cm, chronic total occlusion: 53.2%, bilateral wall calcification: 41.9%) of 1,097 patients with peripheral artery disease (age: 75 ± 9 years, men: 69.4%, diabetes mellitus: 60.8%, chronic kidney disease: 66.2%) undergoing Eluvia (Boston Scientific) drug-eluting stent implantation for femoropopliteal lesions. The primary outcome measure was 1-year restenosis, whereas the secondary outcome measures were 1-year occlusive restenosis, stent thrombosis, target lesion revascularization, and aneurysmal degeneration. The 1-year occurrence rates of restenosis (12.9%), occlusive restenosis (9.2%), stent thrombosis (3.3%), target lesion revascularization (6.2%), and aneurysmal degeneration (16.8%) were found. Multivariate analysis demonstrated that dialysis, chronic limb-threatening ischemia, history of revascularization, a smaller reference vessel diameter, chronic total occlusion, and spot stenting were significantly associated with an increased risk of 1-year restenosis, whereas intravascular ultrasound use and subintimal wire passage were significantly associated with an increased risk of 1-year aneurysmal degeneration. This study documented the 1-year clinical outcomes after femoropopliteal endovascular therapy with FP-DES implantation in real-world practice. The 1-year restenosis rate would be clinically acceptable, whereas the occurrence of occlusive restenosis and aneurysmal degeneration should be noted.

Effect of Crack Patterns in Calcified Plaque on Lumen Area after Stenting for a Severe Calcified Coronary Artery (from the Optical Frequency Domain Imaging-Guided Percutaneous Coronary Artery Intervention for Calcified Lesion Registry).

Background Severely calcified coronary artery stenting remains a challenge due to stent thrombosis, target vessel failure, and higher mortality. Moreover, optimal vessel preparation for calcified plaque with a crack formation pattern has not been established yet. We aimed to identify the effect of crack formation in calcified plaque in the coronary artery on the lumen area after stenting. Materials and Methods We evaluated 50 consecutive patients undergoing drug-eluting stent implantation for severely calcified lesions by using optical frequency domain imaging (OFDI) (54 lesions); we analyzed OFDI image slices every 3 mm and evaluated the segments of 242 images in those who had the arc of calcium more than 180°. Crack formation in calcified plaque was classified into three types: type 0, no cracks; type 1, no dissection between calcified plaque and vessel wall; and type 2, any dissection between calcified plaque and vessel wall. Results Type 2 had a significantly higher area expansion ratio between preballooning and poststenting (type 0, 196% (interquartile range (IQR), 163–244); type 1, 210% (IQR, 174–244); type 2, 237% (IQR, 203–294)). Conclusions The dissection between calcified plaque and vessel wall was a significant factor affecting lumen area expansion after stenting.

Quantification of periaortic adipose tissue in contrast-enhanced CT angiography: technical feasibility and methodological considerations

To examine the feasibility of the quantification of abdominal periaortic fat tissue (PaFT) (tissue within − 45 to − 195 HU) in enhanced CT-angiographies compared to unenhanced CT-scans and identify methodological issues affecting its clinical implementation. Using OsirixMD, PaFT volume and mean HU value were retrospectively measured within a 5 mm periaortic ring in paired unenhanced and enhanced abdominal aortic CT-scans. The correlation between PaFT values was examined in a derivation cohort (n = 101) and linear regression analysis produced correction factors to convert values from enhanced into values from unenhanced CTs. The conversion factors were then applied to enhanced CTs in a different validation cohort (n = 47) and agreement of corrected enhanced values with values from unenhanced scans was evaluated. Correlation between PaFT Volume und Mean HU from enhanced and unenhanced scans was very high (r > 0.99 and r = 0.95, respectively, p < 0.0001 for both). The correction factors for PaFT Volume and Mean HU were 1.1057 and 1.0011. Potential confounding factors (CT-kilovoltage, slice thickness, mean intraluminal contrast density, aortic wall calcification, longitudinal variation of intraluminal contrast density, aortic diameter) showed no significant effect in a multivariate regression analysis (p > 0.05). Bland-Altman analysis of corrected enhanced and unenhanced values showed excellent agreement and Passing–Bablok regression confirmed minimal/no residual bias. PaFT can be quantified in enhanced CT-angiographies very reliably. PaFT Volume scores are very consistently slightly underestimated in enhanced scans by about 10%, while the PaFT Mean HU value remains practically constant and offers distinct methodological advantages. However, a number of methodological issues remain to be addressed.

POS-432 PRIMARY HYPEROXALURIA, A TOO OFTEN MISSED DIAGNOSIS AND CAUSE OF END STAGE KIDNEY DISEASE IN ADULTS : A MONOCENTRIC TUNISIAN STUDY

Primary hyperoxaluria (PH) is a rare hereditary metabolic disorder of oxalate overproduction. Persistently high plasma oxalate concentrations lead to potential life-threatening complications. The major objective of this study is to investigate this condition which is frequent in our country but under diagnosed. In a retrospective descriptive study, we reviewed the record of 9 patients who were diagnosed with primary hyperoxaluria hospitalized at a nephrology department during the period 2001-2020. Their demographics, clinical and investigations parameters were documented. Nine patients were enrolled and followed up. Mean age of patients was 21, 2 ± 12, 3 years with predominance of male (88, 8%). Consanguinity was noted in 28, 5%. All our patients were from Tunisian center (55, 5% were from Gafsa). Renal colic and urolithiasis were the most common symptoms in our study (100%). Ultrasonography and CT scans showed nephrocalcinosis in 5 cases (55, 55%). Urinary tract infections were observed in 2 cases (22, 2%). Renal failure was noted in almost all cases; serum creatinine level ranged from 144 to 986 µmol/L. Seven patients reached end-stage renal disease and were treated with hemodialysis at a median age of 23 years. The extra renal manifestations were bone impairment (4 cases), bone marrow fibrosis (2 cases), cardiac dysfunction (1case), digestive wall calcifications (1 case) and adrenal insufficiency (1 case). The diagnosis was based on Hyperoxaluria (1 case), positive crystalluria (1 case), kidney stone analysis (2 cases) and oxalate crystal deposition identified in both renal and bone marrow biopsy respectively in one and four cases. Mutational analysis of AGXT gene was carried out in five out of nine patients. We identified a novel frameshift mutation in the AGXT gene, the c.406_410dupACTGC resulting in a truncated protein (p.Gln137Hisfs*19). It was found in homozygous state in two related patients from the Tunisian center. Primary hyperoxaluria is not rare in the Tunisian population. In our study it was lately diagnosed in most cases. Awareness campaign to change attitude of family members to screening should be conducted.

Abstract WMP69: Features Of Calcified Carotid Atherosclerosis Are Associated With Stroke In Patients With Embolic Stroke Of Undetermined Source

Introduction: We examined qualitative features of calcified plaque in patients with embolic stroke of undetermined source (ESUS). Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA neck and meeting criteria for ESUS was identified. A segmentation software measured carotid bifurcation calcified plaque volumes. A neuroradiologist manually measured maximum carotid wall and calcified wall thickness (WT), maximum craniocaudal calcified plaque length, degree of circumferential involvement (none, punctate, 90°, 180°, 270°, 360°) and assessed for intimal, transmural, and adventitial calcifications. Descriptive statistics included medians and interquartile ranges. Differences between ipsilateral (carotid ipsi ) and contralateral (carotid contra ) carotid arteries to stroke side were tested using Wilcoxon Signed-Rank, McNemar, and marginal homogeneity tests. Results: Ninety-four subjects met criteria for ESUS. Mean age was 65 years and 55% were women. Carotid ipsi had a significantly higher volume of calcified plaque [Vol ipsi =39.1 (12.4, 86.7) vs Vol contra =25.9 (4.9, 71.7), p=0.05] and maximum calcified WT [CalcWT ipsi= 1.4 (0, 2.6) vs CalcWT contra =0 (0, 2.1), p=0.03] than carotid contra . There were no significant differences in the maximum craniocaudal calcified plaque length (p=0.09) or degree of circumferential calcified plaque involvement (p=0.35) between carotid ipsi and carotid contra . Intimal (p=0.03) but not transmural (p=0.14) or adventitial (p=0.12) calcifications were significantly more frequent in carotid ipsi than carotid contra . A subgroup analysis (n=48) including either carotid artery measuring ≥3mm in maximum WT showed intimal calcifications remained significantly associated with stroke side (p=0.02; Figure). Conclusion: Higher calcified plaque volumes, calcified wall thickness and intimal calcifications may be associated with ischemic stroke in patients with ESUS.

A large series of true pancreaticoduodenal artery aneurysms

IntroductionTrue pancreaticoduodenal artery aneurysms (PDAAs) are rare, and prior reports often fail to distinguish true aneurysms from pseudoaneuryms. We sought to characterize all patients who presented to our health system from 2004 to 2019 with true PDAAs, with a focus on risk factors, interventions, and patient outcomes. MethodsPatients were identified by querying a single health system picture archiving and communication system database for radiographic reports noting a PDAA. A retrospective chart review was performed on all identified patients. Patients with pseudoaneurysm, identified as those with a history of pancreatitis, abdominal malignancy, hepatopancreaticobiliary surgery, or abdominal trauma, were excluded. Continuous variables were compared using t-tests, and categorical variables were compared using Fisher's exact tests. ResultsA total of 59 true PDAAs were identified. Forty aneurysms (68%) were intact (iPDAAs) and 19 (32%) were ruptured (rPDAAs) at presentation. The mean size of rPDAAs was 16.4 mm (median size, 14.0 mm; range, 10-42 mm), and the mean size of iPDAAs was 19.4 mm (median size, 17.5 mm; range, 8-88 mm); this difference was not statistically significant (P = .95). Significant celiac disease (occlusion or >70% stenosis) was noted in 39 aneurysms (66%). Those with rupture were less likely to have significant celiac disease (42% vs 78%; P = .017) and less likely to have aneurysmal wall calcifications (6% vs 53%; P = .002). Thirty-seven patients underwent intervention (63%), with eight (22%) undergoing concomitant hepatic revascularization (two stents and six bypasses) due to the presence of celiac disease. Eighteen patients with occluded celiac arteries underwent aneurysm intervention; of those, 11 were performed without hepatic revascularization (61.1%). Those with rPDAAs experienced an aneurysm-related mortality of 10.5%, whereas those with iPDAAs experienced a rate of 5.6%. One patient with celiac occlusion and PDA rupture who did not undergo hepatic artery bypass expired postoperatively from hepatic ischemia. rPDAAs showed a trend toward the increased need for aneurysm-related endovascular or open reintervention, but this was not statistically significant (47% vs 28%; P = .13). ConclusionsThese findings support previous reports that the rupture risk of PDAAs is independent of size, their development is often associated with significant celiac stenosis or occlusion, and rupture risk appears decreased in patients with concomitant celiac disease or aneurysm wall calcifications. Endovascular intervention is the preferred initial treatment for both iPDAAs and rPDAAs, but reintervention rates are high in both groups. The role for hepatic revascularization remains uncertain, but it does not appear to be mandatory in all patients with complete celiac occlusion who undergo PDAA interventions.

Retained gallstones: A forgotten complication after laparoscopic cholecystectomy

A 68-year-old woman with history of Laparoscopic Cholecystectomy (LC) for symptomatic gallstones 1 month ago, presented to the emergency department for mid abdominal pain since surgery. The pain is severe, continuous and unrelated to food. Her past medical history is significant for Diabetes Mellitus Type 2. On physical examination, she had localized abdominal tenderness and guarding at two surgical sites with skin induration. Laboratory studies were significant for leukocytosis (WBC 15,200) and elevated C- Reactive Protein of 150 mg/L. A contrast enhanced abdominal and pelvic CT scan showed postsurgical changes in the anterior abdominal wall and peritoneal calcification in the anterior aspect of the peritoneal cavity with associated fat stranding (Figure A and B).

Giant Aneurysm Management.

The treatment of giant aneurysms has always been a challenge in the field of neurovascular disease. Giant aneurysms are larger in size and are associated with thrombosis development and the calcification of the aneurysmal wall and neck, which often interfere with direct clipping. Most giant aneurysms have a wide neck with an incomplete thrombus, making complete embolization almost impossible. Giant aneurysms of different sites have entirely different hemodynamic characteristics. Moreover, aneurysms at the same site may exhibit very different hemodynamics among different individuals. Therefore, careful assessment of each case is required before and during treatment to develop and carry out an individualized treatment plan.

Long-standing Renal Hydatid Cyst Mimicking an Angiomyolipoma: A Rare Case Report

Primary hydatid cyst of the kidney is very rare and accounts for 1-4% of all hydatid disease. Authors hereby reports an unusual case of an isolated, long-standing renal hydatid cyst, mimicking an angiomyolipoma on imaging. A 72-year-old female, from a rural area, presented with pain in the right flank since two years. She also complained of mild fever off and on, since one year. A 10×10 cm, non tender lump was palpated in the right flank. Ultrasonography and computerised tomography showed a large rightsided renal mass measuring 10 cms and a diagnosis of angiomyolipoma was rendered. A right sided open/simple nephrectomy was done. The kidney was large, cystic, firm and was sent for histopathological examination. On gross examination, a large, unilocular, thick- walled, cystic lesion was seen. Cut-surface showed heterogeneous, creamy coloured necrotic contents, with few nodular gelatinous masses. On microscopy, characteristic acellular, laminated structure of the ectocyst of Echinococcus granulosus was seen. Extensive calcification and ossification of the cyst wall with bone marrow production was also seen. Contents of the cyst were necrotic and no daughter cysts were seen. Adipose tissue of the bone marrow was mistaken on imaging for the lipomatous component of an angiomyolipoma. Isolated renal hydatid cyst is very uncommon and though active hydatid cysts do have characteristic radiological findings, they can be misdiagnosed as a benign renal tumours. Renal cysts or abscesses. Old cases show degenerative changes as well as calcification and are difficult to diagnose preoperatively. Surgical treatment of renal hydatid cyst depends on the size, number of cysts, exact intrarenal location and residual renal function.

Surgical tracheoplasty for children with congenital tracheal stenosis undergoing previous balloon dilatation or tracheal metal stent placement: a series of 9 cases

Objective: To examine the outcomes of Slide tracheoplasty for the children with severe congenital tracheal stenosis received previous repeated balloon dilatation or metal stent placement under endoscopy. Methods: A retrospective study was conducted in 9 children with congenital tracheal stenosis undergoing previous interventional therapy under tracheoscopy and later received Slide tracheoplasty due to obvious respiratory symptoms at Department of Cardiac Surgery, Qilu Children's Hospital of Shandong University between February 2017 and July 2021. There were 7 males and 2 females with a median age at operation of 72.4 months (range: 13.3 to 98.9 months), and the median weight was 19.0 kg (range: 9.0 to 33.0 kg). Among the 9 patients, 2 patients began to receive repeated balloon dilatation (more than 3 times) 17.8 and 51.8 months ago respectively. One patient received metal stents placement into the trachea for 4 days and the other 6 children for median 56.8 months (range: 21.6 to 74.2 months). Complete tracheal cartilage rings and long segmental stenosis were present. in all 9 children. Operative details and outcome measures, including the need for endoscopic airway intervention and mortality, were collected. Results: Slide tracheoplasty was performed in all cases. Two patients with repeated balloon dilatation had different thickness of tracheal wall, local scar hyperplasia and irregular lumen. Among them, 1 case had obvious local calcification of tracheal wall, which was difficult to suture. The metal stent in one patient with short time of placement was completely removed. However, only part of the metal stents could be removed due to the long placement time in the other 6 cases. There was no operative death in the 9 children. The median postoperative tracheal intubation time was 25.3 hours (range: 17.4 to 74.5 hours). A silicone stent was placed in the trachea of 1 child due to obvious respiratory symptoms. Follow-up of median 11 months (range: 1 to 23 months) showed that no death occurred after discharge and all children had basically normal activity tolerance with no obvious respiratory symptoms. Conclusions: Slide tracheoplasty is feasible for children undergoing prior balloon dilatation or metal stents placement. Previously repeated balloon dilatation or metal stent placement under endoscopy increased the difficulty of slide tracheoplasty, the metal stent could not be completely removed after a long time.

Aortic aneurysm associated with rheumatoid aortitis

A 59-year-old female, presented with dry cough, burning micturition with urgency and frequency for 2 months. She was known to have hypertension, hypothyroidism and rheumatoid arthritis for the past 30 years; and was receiving oral methotrexate 20 mg per-week. She also had complianed of low backache for 2 months. No phenotypic features of Marfans/Ehler Danlos were evident. Cardiovascular system examination was unremarkable. Chest radiograph showed mediastinal widening with a large fusiform descending thoracic aortic aneurysm. Computed tomography (CT) of the chest showed subpleural fibrosis and fusiform dilatation of the aorta from the origin till the supracoeliac aorta. CT aortogram revealed an irregular non-enhancing wall thickening and calcification of the aorta with fusiform dilatation (4.5 cm × 4.6 cm in the ascending aorta and 4.4 cm × 4.3 cm in the distal descending aorta). The patient did not have any features of giant cell arteritis (GCA)/Takayasu's arteritis; Venereal Disease Research Laboratory (VDRL) test was negative. The patient was diagnosed to have aortic regurgitation due to long standing rheumatoid arthritis and was referred to the department of cardiothoracic and vascular surgery for further management.

Reconstruction of Calcified Hepatic Artery in the Donor Liver: A Case Report

The transplant teams may even push the boundaries outside the norm to ensure optimal outcome from donation. An offer of liver graft from 58 years old female DBD donor was accepted. Donor history entailed type I diabetes mellitus, hypertension and previous hemodialysis, before undergoing cadaveric renal transplant. A male recipient with cryptogenic cirrhosis and HCC with UKELD of 58, was selected as the recipient. The organ was retrieved by a different surgical team, once the images of the liver were received and the retrieval team reported no anomalies or injuries, recipient hepatectomy was stared prior to the graft arrival in order to keep the cold ischemia time as short as possible. On back table dissection of the liver graft it was identified that the donor common hepatic artery was heavily calcified. As the recipient was already anhepatic therefore after careful consideration it was decided to precede with the implantation of the donor liver. Recipient CHA was prepared at the GDA junction and corresponding CHA/GDA patch on the graft. A 5mm diameter extruding calcified plaque was excised from the site of the anastomosis but most of the circumference of graft patch had integrated wall calcification which could not be excised. On table Doppler USS suggested extensive intrahepatic calcification but excellent traces after arterial reconstruction. The Peak systolic volume was >60cm. Graft function was evident by good bile production, normal TEG, INR and lactate clearance. We believe that hepatic artery atherosclerosis on its own is not an absolute contraindication to liver transplantation.

Outcomes of Microsurgical Clipping in Middle Cerebral Artery Aneurysms

Objective: Surgical or endovascular treatment is used in the treatment of intracranial aneurysms. Recent studies have suggested that the of endovascular treatment are superior to surgery Middle cerebral artery (MCA) aneurysm is the third most common bleeding aneurysm after anterior communicating artery and internal carotid artery aneurysms. We aimed to retrospectively evaluate the microsurgical outcomes of cases operated for MCA aneurysm.Methods: Twenty cases with MCA aneurysm who accepted the microsurgical treatment option were included in this study. Data were obtained by retrospectively reviewing the clinical, radiological, and intraoperative findings, as well as postoperative morbidity and mortality of the cases.Results: In total, 23 MCA aneurysms were detected in 20 cases. In 2 cases, MCA aneurysm was detected incidentally. Microsurgical clipping was performed in 23 aneurysms. In the study, the total mortality rate was 10% and the morbidity rate was 20% in MCA aneurysms.Conclusion: It was observed that the incidence of calcification or thrombosis within the aneurysm increased and the Glasgow outcome scores at the 3rd month decreased as the width and length values of the aneurysm sac increased. In addition, presence of calcification in the aneurysm wall or thrombosis in the sac was found to be positive and strongly correlated with mortality and morbidity.

Stressor-Induced "Inflammaging" of Vascular Smooth Muscle Cells via Nlrp3-Mediated Pro-inflammatory Auto-Loop.

Calcification of the vessel wall as one structural pathology of aged vessels is associated with high cardiovascular mortality of elderly patients. Aging is linked to chronic sterile inflammation and high burden of reactive oxygen species (ROS), leading to activation of pattern recognition receptors (PRRs) such as Nlrp3 in vascular cells. The current study investigates the role of PRR activation in the calcification of vascular smooth muscle cells (VSMCs). Therefore, in vitro cell culture of primary rat VSMCs and ex vivo aortic stimulations were used to analyze osteogenic, senescence and inflammatory markers via real-time PCR, in situ RNA hybridization, Western Blot, photometric assays and histological staining. Induction of ROS and DNA-damage by doxorubicin induces a shift of VSMC phenotype toward the expression of osteogenic, senescence and inflammatory proteins. Induction of calcification is dependent on Nlrp3 activity. Il-1β as a downstream target of Nlrp3 induces the synthetic, pro-calcifying VSMC phenotype. Inhibition of PRR with subsequent reduction of chronic inflammation might be an interesting target for reduction of calcification of VSMCs, with subsequent reduction of cardiovascular mortality of patients suffering from vessel stiffness.

The prognostic impact of vascular calcification on abdominal aortic aneurysm progression

ObjectiveThe maximal aortic diameter is currently the only clinically applied predictor of abdominal aortic aneurysm (AAA) progression. It is known that the risk of rupture is associated with aneurysm size; hence, accurate monitoring of AAA expansion is crucial. Aneurysmal vessel wall calcification and its implication on AAA expansion are insufficiently explored. We evaluated the vascular calcification using longitudinal computed tomography angiographies (CTA) of patients with an AAA and its association with AAA growth. MethodsWe conducted a retrospective study of 102 patients with an AAA with a total of 389 abdominal CTAs at 6-month intervals, treated and followed at the Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna. Digitally stored CTAs were reviewed for vascular calcification (volume and score) of the infrarenal aorta and common iliac arteries as well as for morphometric AAA analysis. In the prognostic setting, slow versus fast AAA progression was defined as a less than 2 mm or a 2-mm or greater increase in AAA diameter over 6 months. In addition, to analyze the association of vascular calcification and the AAA growth rate with longitudinal monitoring data, a specifically tailored log-linear mixed model was used. ResultsAn inverse relation of increased abdominal vessel wall calcification and short-term AAA progression was detected. Compared with fast progressing AAA, the median calcification volume of the infrarenal aorta (1225.3 mm³ vs 519.8 mm³; P = .003), the median total calcification volume (2014.1 mm³ vs 1434.9 mm³; P = .008), and the median abdominal total customized Agatston calcium (cAC) score (1663.5 vs 718.4; P = .003) were significantly increased in slow progressing AAA. Importantly, a log-linear mixed model efficiently predicted AAA expansion based on current diameter and abdominal total cAC score (P = .042). ConclusionsWe assessed the prognostic value of CTA-measured vascular calcification for AAA progression. Increased vascular calcification stabilizes the aortic aneurysmal wall and likely protects against progressive AAA expansion, resulting in a significant decrease of aneurysm growth over time. As a consequence, this may have implications for rupture risk, mortality, morbidity, and cost.

Matrix Gla-protein expression in peripheral blood mononuclear cells is related to risk factors in cardiovascular diseased patients

Abstract Objectives Matrix Gla protein (MGP) is a calcification inhibitor that plays a role in preventing soft tissue calcification and local mineralization of the vascular wall. The present study aimed to assess the expression of MGP in Peripheral Blood Mononuclear Cells (PBMC) in adult patients with CVD pathologies and its association with the presence and severity of coronary artery calcium score (CACS) and conventional CVD risk factors. Methods MGP expression was measured in 87 individuals using real time qPCR. Subgrouping was performed according etiologic and metabolic CVD risk factors. Results A clear trend for a decreased MGP expression was observed in all subgroups with high CVD risk. This decrease was significant in abdominally obese hypertensive individuals and in those with dyslipidemia. MGP expression was significantly lower in patients representing high Total cholesterol and LDL cholesterol levels. A positive correlation between MGP expression and smoking status in patients with coronary calcium and in the CVD group was established. Atrial hypertension duration correlated negatively with MGP expression in the group without coronary calcium deposits. Conclusions The current study supports the hypothesis that MGP expression in PBMC probably reflects CVD pathology and is related to lipid metabolism dysregulation.

Local aortic aneurysm wall expansion measured with automated image analysis

BackgroundAssessment of regional aortic wall deformation (RAWD) might better predict for abdominal aortic aneurysm (AAA) rupture than the maximal aortic diameter or growth rate. Using sequential computed tomography angiograms (CTAs), we developed a streamlined, semiautomated method of computing RAWD using deformable image registration (dirRAWD). MethodsPaired sequential CTAs performed 1 to 2 years apart of 15 patients with AAAs of various shapes and sizes were selected. Using each patient’s initial CTA, the luminal and aortic wall surfaces were segmented both manually and semiautomatically. Next, the same patient’s follow-up CTA was aligned with the first using automated rigid image registration. Deformable image registration was then used to calculate the local aneurysm wall expansion between the sequential scans (dirRAWD). To measure technique accuracy, the deformable registration results were compared with the local displacement of anatomic landmarks (fiducial markers), such as the origin of the inferior mesenteric artery and/or aortic wall calcifications. Additionally, for each patient, the maximal RAWD was manually measured for each aneurysm and was compared with the dirRAWD at the same location. ResultsThe technique was successful in all patients. The mean landmark displacement error was 0.59 ± 0.93 mm with no difference between true landmark displacement and deformable registration landmark displacement by Wilcoxon rank sum test (P = .39). The absolute difference between the manually measured maximal RAWD and dirRAWD was 0.27 ± 0.23 mm, with a relative difference of 7.9% and no difference using the Wilcoxon rank sum test (P = .69). No differences were found in the maximal dirRAWD when derived using a purely manual AAA segmentation compared with using semiautomated AAA segmentation (P = .55). ConclusionsWe found accurate and automated RAWD measurements were feasible with clinically insignificant errors. Using semiautomated AAA segmentations for deformable image registration methods did not alter maximal dirRAWD accuracy compared with using manual AAA segmentations. Future work will compare dirRAWD with finite element analysis–derived regional wall stress and determine whether dirRAWD might serve as an independent predictor of rupture risk.