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

2021 ◽  
pp. 1-9
Author(s):  
Vladimir N. Melnikov ◽  
Lena B. Kim ◽  
Anna N. Putyatina ◽  
Sergey G. Krivoschekov

<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.

1993 ◽  
Vol 120 (3) ◽  
pp. 799-814 ◽  
Author(s):  
A Streit ◽  
C Nolte ◽  
T Rásony ◽  
M Schachner

We have recently characterized a chondroitin sulfate proteoglycan from the murine central nervous system which is expressed by astrocytes in vitro and carries the L2/HNK-1 and L5 carbohydrate structures. In the present study, we provide evidence that its three core proteins of different size are similar in their proteolytic peptide maps and thus designate this group of structurally related molecules astrochondrin. During development, astrochondrin and the L5 carbohydrate were hardly detectable in the brain of 14-d-old mouse embryos by Western blot analysis. Expression of astrochondrin and the L5 epitope was highest at postnatal day 8, the peak of cerebellar granule cell migration and Bergmann glial process formation, and decreased to weakly detectable levels in the adult. Immunocytochemical localization of astrochondrin in the cerebellar cortex of 6-d-old mice showed association of immunoreactivity with the cell surface of astrocytes, including Bergmann glial processes and astrocytes in the internal granular layer or prospective white matter. Endfeet of astrocytes contacting the basal lamina of endothelial and meningeal cells and contact sites between Bergmann glial processes and granule cells also showed detectable levels of astrochondrin. Furthermore, granule cell axons in the molecular layer were astrochondrin immunoreactive. In the adult, astrochondrin immunoreactivity was weakly present in the internal granular layer and white matter. Both Fab fragments of polyclonal antibodies to astrochondrin and monovalent fragments of the L5 monoclonal antibody reduced the formation of processes of mature GFAP-positive astrocytes on laminin and collagen type IV, but not on fibronectin as substrata. Interestingly, the initial attachment of astrocytic cell bodies was not disturbed by these antibodies. Antibodies to astrochondrin also reduced the migration of granule cells in the early postnatal mouse cerebellar cortex. In a solid phase radioligand binding assay, astrochondrin was shown to bind to the extracellular matrix components laminin and collagen type IV, being enhanced in the presence of Ca2+, but not to fibronectin, J1/tenascin or other neural recognition molecules. Furthermore, astrochondrin interacted with collagen types III and V, less strongly with collagen types I, II, and IX, but not with collagen type VI. The interaction of astrochondrin with collagen types III and V was saturable and susceptible to increasing ionic strength, and could be competed by chondroitin sulfate, heparin, and dextran sulfate, but not by hyaluronic acid, glucose-6-phosphate, or neuraminic acid.(ABSTRACT TRUNCATED AT 400 WORDS)


1994 ◽  
Vol 72 (3) ◽  
pp. 449-454
Author(s):  
Dominic S. Raso ◽  
Louis Terracio ◽  
Thomas K. Borg

The distribution of laminin, collagen type IV, collagen bundles, proteoglycans, elastin, and periodic acid–Schiff's moieties (glycoproteins) within the heart of the adult white bass, Morone chrysops (Rafinesque), was investigated by means of immunohistochemical and histological techniques. Laminin and collagen type IV were heavily expressed within the epimysium and the basal lamina of the lining epicardial epithelium and valvular endothelium, moderately expressed within the myocardium, and slightly expressed within the subendocardium. This co-localized distribution of laminin and collagen type IV corresponds to the biochemically unidentified basal and external lamina observed in the hearts of other fish by previous ultrastructural investigations and is similar to the distribution observed in the hearts of birds and mammals. Also demonstrated was an interesting division of connective tissue components along the longitudinal axis of the atrioventricular valve, which is most likely intimately involved with the effective functioning and durability of the valve.


2021 ◽  
Vol 73 (1) ◽  
pp. 103-110
Author(s):  
Braca Kundalic ◽  
Sladjana Ugrenovic ◽  
Ivan Jovanovic ◽  
Vladimir Petrovic ◽  
Aleksandar Petrovic ◽  
...  

The aim of this study was to analyze the expression of extracellular matrix (ECM) proteins in human endoneurium during aging. We harvested 15 cadaveric sural nerves, distributed in 3 age groups (I: 25-44, II: 45-64, III: 65-86 years old). Histological sections were stained immunohistochemically for the presence of collagen type I, type IV and laminin, and the ImageJ processing program was used in morphometrical analysis to determine the percentages of these endoneurial proteins. In two younger groups, the endoneurial matrix of the sural nerve was composed from about equal proportions of these proteins, which may be considered a favorable microenvironment for the regeneration of nerve fibers. Linear regression analysis showed a significant increase in endoneurial collagen type IV with age, while collagen type I and laminin significantly decreased during the aging process. In cases older than 65 years, remodeling of the endoneurial matrix was observed to be significantly higher for the presence of collagen type IV, and lower for the expression of collagen type I and laminin. This age-related imbalance of ECM proteins could represent a disadvantageous microenvironment for nerve fiber regeneration in older adults. Our findings contribute to the development of therapeutic approaches for peripheral nerve regeneration.


2004 ◽  
Vol 24 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Adrian Covic ◽  
David J.A. Goldsmith ◽  
Laura Florea ◽  
Paul Gusbeth–Tatomir ◽  
Maria Covic

Background Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (AIx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and AIx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. Objective To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in AIx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. Results CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 ± 1.09 m/second in CAPD patients, significantly higher ( p < 0.05) compared to HD subjects (7.19 ± 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 ± 1.62 m/s) and essential hypertensive controls (6.34 ± 1.32 m/s), p < 0.05. The AIx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in AIx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. Conclusion CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.


1992 ◽  
Vol 119 (6) ◽  
pp. 1721-1728 ◽  
Author(s):  
V M Paralkar ◽  
B S Weeks ◽  
Y M Yu ◽  
H K Kleinman ◽  
A H Reddi

Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-beta (TGF-beta) family. Both BMP 2B and activin A, but not TGF-beta 1, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited approximately 2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, including fibronectin, laminin, and collagen type IV potentiated the activity of BMP and activin A, with the latter being the most active. Direct experiments demonstrated that radioiodinated BMP 2B bound to collagen type IV better than to either laminin or fibronectin. These data demonstrate a common neurotrophic activity of both BMP 2B and activin A, and suggest that these regulatory molecules alone and in conjunction with extracellular matrix components may play a role in both the development and repair of nervous tissue.


2003 ◽  
Vol 71 (2) ◽  
pp. 1008-1010 ◽  
Author(s):  
Bradford S. McGwire ◽  
Kwang-Poo Chang ◽  
David M. Engman

ABSTRACT Leishmania species engineered to express high levels of the surface metalloprotease gp63 have enhanced capacity of migration through extracellular matrix in vitro. This correlates with gp63 degradation of extracellular matrix components, such as collagen type IV and fibronectin, and suggests an important role for gp63 in the pathogenesis of leishmaniasis.


2007 ◽  
Vol 98 (11) ◽  
pp. 963-969 ◽  
Author(s):  
Dorothe Burggraf ◽  
Helge Martens ◽  
Martin Dichgans ◽  
Gerhard Hamann

SummaryAlthough recombinant tissue plasminogen activator (rt-PA) is successfully used for thrombolysis in human stroke, it may increase the risk of haemorrhagic complications. It was shown that the matrix metalloproteinase (MMP) system is critically involved in basal lamina degradation after middle cerebral artery occlusion and reperfusion following rt-PA administration. We describe the effects of different doses of rt-PA (saline, 0.9, 9, or 18 mg rt-PA/kg body weight) on the MMPs, their specific inhibitors (TIMPs), and also their inducer protein EMMPRIN following experimental cerebral ischemia (3 hours [h], 24 h reperfusion, suture model) in rats. The amount of MMP-2 and -9 was measured by gelatine zymography, TIMP-1 and -2 by reverse gelatine zymography, and the content of EMMPRIN and the basal lamina component collagen type IV by Western blotting. The amount of both MMPs steadily rose with increasing doses of rt- PA (p<0.05). In contrast, their endogenous inhibitors TIMPs decreased (p<0.001). A balance between the proteases and their inhibitors was achieved at the low dose of 0.9 mg/kg rt-PA in the rats, which significantly coincided with the demonstrated protection of collagen type IV degradation at this dose. The inducer protein EMMPRIN increased in parallel to its substrate MMP-2. Exogenous rt-PA leads to an increase of the MMP-inducing system by EMMPRIN, and a rise of the degrading MMPs follows. However, at low to moderate doses of rt-PA the microvascular basal lamina was protected, probably due to inhibition of MMP-2 and MMP-9 by the upregulation of their inhibitors. This strongly supports use of the lowest effective dosage of rt-PA available.


2005 ◽  
Vol 109 (1) ◽  
pp. 103-107 ◽  
Author(s):  
Beatrix MERSICH ◽  
János RIGÓ ◽  
Csilla BESENYEI ◽  
Zsuzsanna LÉNÁRD ◽  
Péter STUDINGER ◽  
...  

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index β, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8±0.2 versus 2.9±0.3 mmHg for Einc), which was reversed after delivery (2.3±0.2 mmHg). Aortic PWV decreased during pregnancy (6.2±0.2 versus 5.4±0.2 m/s) and increased in the PP period (6.7±0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.


2010 ◽  
Vol 298 (2) ◽  
pp. H320-H330 ◽  
Author(s):  
Julio A. Chirinos ◽  
Patrick Segers ◽  
Amresh Raina ◽  
Hassam Saif ◽  
Abigail Swillens ◽  
...  

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P ≤ 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (β = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (β = −17.85; P < 0.0001) during handgrip, Zc during handgrip (β = −150; P < 0.0001), and the change in the timing of wave reflections during handgrip (β = −0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.


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