Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types.

Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.

3-D Contrast-Enhanced Fusion Ultrasound for Accurate Volume Assessment of Vessel Lumen and Plaque in Carotid Artery Disease as Compared With Computed Tomography Angiography.

OBJECTIVE: Three-dimensional contrast-enhanced fusion ultrasound (CEFUS) of atherosclerotic carotid arteries provides spatial visualization of the vessel lumen, creating a lumenography. As in 3-D computed tomography angiography (CTA), 3-D CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3-D CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. Three-dimensional CEFUS is unproven in intermodality studies, vindicating the assessment of 3-D CEFUS applicability and comparing 3-D CEFUS and 3-D CTA lumenography as a proof-of-concept study. METHODS: Using an ultrasound system with magnetic tracking, a linear array transducer and SonoVue contrast agent, 3-D CEFUS acquisitions were generated by spatial stitching of serial 2-D images. From 3-D CEFUS and 3-D CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software program for lumen and plaque volume quantification. Bland-Altman analysis was used for inter-image modality agreement. RESULTS: The study included 39 carotid arteries. Mean lumen and plaque volume in 3-D CEFUS were 0.63 cm3 (standard deviation [SD]: 0.26) and 0.62 cm3 (SD: 0.26), respectively. Lumen volume differences between 3-D CEFUS and 3-D CTA were non-significant, with a mean difference of 0.01 cm3 (SD: 0.02, p = 0.26) and limits of agreement (LoA) range of ±0.11 cm3. Mean plaque volume difference was -0.12 cm3 (SD: 0.19, p = 0.006) with a LoA range of ±0.39 cm3. CONCLUSION: There was strong agreement in lumenography between 3-D CEFUS and 3-D CTA. The interimage modality difference in plaque volumes was substantial because of challenging vessel wall definition in 3-D CTA. Three-dimensional CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.

Acute complications in the post-anaesthesia care unit after infrainguinal surgery for lower limb ischaemia - a prospective observational cohort study.

BACKGROUND: Arterial surgery for lower limb ischaemia is a frequently performed procedure in patients with severe cardio-pulmonary comorbidities, making them high-risk patients for acute postoperative complications with a need for prolonged stay in the post-anaesthesia care unit (PACU). However, detailed information on complications during the PACU stay is limited, hindering mechanism-based interventions for early enhanced recovery. Thus, we aimed to systematically describe acute complications and related risk factors in the immediate postoperative phase after infrainguinal arterial surgery. PATIENTS AND METHODS: Patients transferred to the PACU after infrainguinal arterial surgery due to chronic or acute lower limb ischaemia were consecutively included in a six-month observational cohort study. Pre- and intraoperative data included comorbidities as well as surgical and anaesthetic technique. Data on complications and treatments in the PACU were collected every 15 minutes using a standardised assessment tool. The primary endpoint was occurrence of predefined moderate or severe complications occurring during PACU stay. RESULTS: In total, 155 patients were included for analysis. Eighty (52 %) patients experienced episodes with oxygen desaturation (< 85 %) and moderate or severe pain occurred in 72 patients (47 %); however, circulatory complications (hypotension, tachycardia) were rare. Preoperative opioid use was a significant risk factor for moderate or severe pain in PACU (59 vs. 38 % chronic vs. opioid naïve patients (P = 0.01). CONCLUSIONS: Complications in the PACU after infrainguinal arterial surgery relates to saturation and pain, suggesting that future efforts should focus on anaesthesia and analgesic techniques including opioid sparing regimes to enhance early postoperative recovery.