Center-To-Periphery Arterial Stiffness Gradient Is Attenuated and/or Reversed in Pregnancy-Associated Hypertension

Background: Non-pregnant (NP) women have a progressive increase in arterial stiffness from central-to-peripheral arteries [“stiffness gradient” (SG)], which is of physiologic importance since excessive pulsatility is filtered by the creation of wave reflections. If the aorta gets stiff with minimal or no change in the periphery, the SG is dissipated transmitting pressure disturbances to the microcirculation. It remains unknown the status of the SG in both women with healthy pregnancies (HP) and complicated by pregnancy-associated hypertension (PAH).Objective: To determine whether HP and PAH are associated with changes in SG. Secondarily, we aim at identifying potential differences between the subgroups of PAH (pre-eclampsia and gestational hypertension).Methods: HP (n = 10), PAH (n = 16), and healthy NP women (n = 401, to be matched for age, and cardiovascular risk with the pregnant women) were included. Carotid-to-femoral (cfPWV) and carotid-to-radial pulse wave velocity (crPWV), common carotid artery (CCA) and brachial artery (BA) diameters and elastic modulus (EM), and regional (cfPWV/crPWV or “PWV ratio”) and local (CCA EM/BA EM or “EM ratio”) SG were quantified.Results: HP showed no changes in PWV ratio compared with NP, in the presence of significantly lower cfPWV and crPWV. HP exhibited higher arterial diameters and lower CCA EM/BA EM compared to NP, without differences with PAH. PAH was associated with a significant increase in the PWV ratio that exceeded the levels of both NP and HP, explained by a lower (although significant) reduction of cfPWV with respect to that observed in HP with respect to NP, and a higher reduction in crPWV with respect to that observed between HP and NP. The blunted reduction in cfPWV observed in PAH coincided with an increase in the CCA EM.Conclusions: Compared with NP, HP was associated with unchanged PWV ratio but with a reduction in CCA EM/BA EM, in the setting of a generalized drop in arterial stiffness. Compared with NP and HP, PAH was associated with an “exaggerated rise” in the PWV ratio without changes in CCA EM/BA EM, in the setting of a blunt reduction in cfPWV but exaggerated crPWV drop. The SG attenuation/reversal in PAH was mainly driven by pre-eclampsia.

Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.

Comparative lipid profiling of murine and human atherosclerotic plaques using high-resolution MALDI MSI

The distribution of atherosclerotic lesions in the aorta and its branches of ApoE knockout (ApoE−/−) mice is like that of patients with atherosclerosis. By using high-resolution MALDI mass spectrometry imaging (MSI), we aimed at characterizing universally applicable physiological biomarkers by comparing the murine lipid marker profile with that of human atherosclerotic arteries. Therefore, the aorta or carotid artery of male ApoE−/− mice at different ages, human arteries with documented atherosclerotic changes originated from amputated limbs, and corresponding controls were analysed. Obtained data were subjected to multivariate statistical analysis to identify potential biomarkers. Thirty-one m/z values corresponding to individual lipid species of cholesterol esters, lysophosphatidylcholines, lysophosphatidylethanolamines, and cholesterol derivatives were found to be specific in aortic atherosclerotic plaques of old ApoE−/− mice. The lipid composition at related vessel positions of young ApoE−/− mice was more comparable with wild-type mice. Twenty-six m/z values of the murine lipid markers were found in human atherosclerotic peripheral arteries but also control vessels and showed a more patient-dependent diverse distribution. Extensive data analysis without marker preselection based on mouse data revealed lysophosphatidylcholine and glucosylated cholesterol species, the latter not being detected in the murine atherosclerotic tissue, as specific potential novel human atherosclerotic vessel markers. Despite the heterogeneous lipid profile of atherosclerotic peripheral arteries derived from human patients, we identified lipids specifically colocalized to atherosclerotic human tissue and plaques in ApoE−/− mice. These data highlight species-dependent differences in lipid profiles between peripheral artery disease and aortic atherosclerosis.

INFLUENCE OF VARIOUS SURGICAL INTERVENTIONS ON VASCULAR WALL APOPTOSIS INDICES IN PATIENTS WITH ATHEROSCLEROSIS OF PERIPHERAL ARTERIES

Objective. Assessment of apoptosis proteins Bcl-2 and Bax indices before and after the open vascular reconstructions and X-ray endovascular interventions in patients with the peripheral atherosclerosis of the arteries of the lower extremities. Methods. The study included patients (n=40) with the peripheral atherosclerosis of the lower extremities arteries (stage III-IV) disease who underwent open surgery - group A, and patients (n=40) who underwent endovascular interventions - group B. Two apoptosis proteins were analyzed in blood serum: Bax and Bcl-2 initially before surgery, on the 1^st day and after 1 month. The reference values of the studied parameters were determined in 40 healthy volunteers. Results. Initial Bax protein index - 27.1 ng / ml (р<0,001) were elevated in patients of group A and reduced Bax protein - 4.4 ng / ml (p=0.00008) in patients of group B compared with indices of healthy volunteers (16.5 ng / ml, 5.3 ng / ml, respectively). On the 1^st day after the interventions in the patients of the operative groups there was an increasing tendency for Bax index to 35.6 ng / ml (p<0.001) - group A, to 25.6 ng/ml (p<0.001) - group B. By the end of 1^st month, Bax was increased to 28 ng/ml (p<0.001) in patients of group A and Bcl-2 was reduced to 3.0 ng / ml (p=0.039) compared to the initial indices; in patients of group B, only protein Bax - 23.9 ng / ml (p<0.001) was increased. Conclusion. Open and endovascular intervention on the arteries of the lower extremities leads to the activation of the pro-apoptotic protein Bax on the 1^st day after surgery. In the postoperative period the open reconstruction leads to an evaluation of the pro-apoptotic potential in comparison with endovascular intervention in the form of increasing Bax protein and reducing Bcl-2 by the end of the first month. What this paper adds The dynamics of changes markers Bcl-2 and Bax in apoptosis at different periods after surgery has been firstly studied in patients with atherosclerosis of peripheral arteries (stage III-IV) of the lower extremities. It has been found that the open surgery leads to a sufficient evaluation of the proapoptotic potential, i.e. the increasing Bax protein index on the 1^st day and by the end of 1^st month with reducing Bcl-2 index by the end of 1^st month compared with the endovascular intervention.

Preclinical Evaluation of the Temporary Drug-Coated Spur Stent System in Porcine Peripheral Arteries

Background: Drug penetration into the deeper arterial wall of heavily calcified lesions is one of the limitations of drug-coated balloons and drug-eluting stents in vascular interventions. The Temporary Spur Stent (TSS) system is characterized by a self-expanding nitinol stent that is uniformly covered in radialspikes, which, when coated, should allow a deeper penetration and longer retention of the drug into the diseased artery walls by penetrating through the calcified plaques. Materials and Methods and Results: Uncoated TSS and paclitaxel (PTX)-coated TSS systems have been deployed in porcine peripheral arteries. Four weeks after the deployment of uncoated TSS systems, no adverse vascular remodeling or neointimal formation in the treated vessel segments were noticed. PTX-coated TSS systems transferred 9%±7% of the drug that was on the device to the targeted vessel area (196±163 ng PTX/mg arterial tissue) and the addition of the fluorescent dye Nile red to the coating showed that the spikes promote the transfer of the coating to the deeper layers of the vessel wall. The PTX-coated TSS systems showed a significant reduction in neointimal proliferation compared to the uncoated TSS systems: quantitative angiography showed a vessel diameter stenosis of 37.2%±11.0% and 16.4%±8.8% 4 weeks after the treatment with uncoated and PTX-coated TSS systems, respectively. Conclusion: The treatment with the TSS system was well tolerated and the spikesfacilitate the transfer of the coating into deeper layers of the vessel wall. Moreover, the PTX-coated TSS systems effectively inhibit neointimal proliferation.

Association of Circulating Extracellular Matrix Components with Central Hemodynamics and Arterial Distensibility of Peripheral Arteries

<b><i>Background:</i></b> In addition to neuronal and endothelial regulators of vascular tone, the passive mechanical properties of arteries, determined by the molecular structure of extracellular matrices, are the principle modulators of vascular distensibility. Specifically, the association between collagen type IV (Col IV), a constituent of basement membrane, and arterial compliance remains unclear. <b><i>Methods:</i></b> In 31 healthy adult men, radial applanation tonometry and pulse wave analysis were used to assess aortic augmentation index (AIx), aortic-to-radial pulse pressure amplification (PPAmpl), and time to reflection wave. <b><i>Results:</i></b> Plasma Col IV and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) concentrations were correlated with AIx (<i>r</i> = 0.51, <i>p</i> = 0.021 and <i>r</i> = −0.45, <i>p</i> = 0.042, respectively) after adjustment for age and heart rate (HR). Greater matrix metalloproteinase-9 (MMP-9) and TIMP-1 levels were associated with high PPAmpl (<i>r</i> = 0.45 and <i>r</i> = 0.64, respectively) and hence with compliant arteries. Multiple regression analyses revealed that 99% of the variation in PPAmpl was attributable to age, HR, Col IV, TIMP-1, and Col × TIMP-1 interaction (<i>p</i> &#x3c; 0.001). No relations between tonometric variables and levels of MMP-1, -2, and -3; TIMP-2 and -4; fibronectin; glycosaminoglycans; and hydroxyproline were found. <b><i>Conclusion:</i></b> High circulating Col IV level indexes were associated with stiffer peripheral arteries whereas increased MMP-9 and TIMP-1 concentrations were associated with more compliant ones.