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Gerard Pasterkamp

Publications and source records attributed to Gerard Pasterkamp.

At least 19 recordsLinked to original sources
PubMed2026

Sex-specific associations of the plasma-proteome with incident coronary artery disease.

AIMS: The etiology of coronary artery Disease (CAD) appears different for men and women, yet insights into underlying sex-specific biological mechanisms are limited. We integrated genomic and proteomic analyses to investigate sex-specific associations of the plasma-proteome with CAD. METHODS AND RESULTS: In 40,829 UK Biobank participants (free-of-CAD, baseline-365 days thereafter; 55% women; mean age 56.9&#x2009;&#xb1;&#x2009;8.1 years), we examined associations between 2,922 plasma proteins and incident CAD over a median follow-up of 13.7 years (IQR 13.1-14.4) using multivariable-adjusted Cox proportional hazards models. Sex-specific analyses identified 440 female exclusive and 32 male exclusive proteins associated with incident CAD (FDR-corrected p&#x2009;<&#x2009;0.05), revealing distinct pathway enrichments, including innate immune response in women and angiogenesis in men. Causality was assessed through combined and sex-stratified two-sample Mendelian randomization (MR) using inverse-variance-weighted analyses with genome wide association summary statistics from 422,108 men (61,969 cases) and 521,695 women (27,128 cases) (UK Biobank, FinnGen freeze 9). Integration of direct sex-protein interaction analyses with sex-combined MR identified 59 proteins with evidence for sex-specific causal effects. Four proteins demonstrated concordant directionality in sex-stratified MR analyses (n&#x2009;=&#x2009;943,803) and multivariable regression models, namely CDKN2D, MYH9, and SKAP2 (women), and CTSH (men). To assess translational relevance, prioritized targets were further evaluated in secondary major adverse cardiovascular events among carotid endarterectomy patients (MACE; Athero-Express) and acute myocardial infarction (AMI; MISSION!) using plasma proteomics and ELISA. After further top-target identification in the context of MACE and AMI, clinical drug candidates were identified through a machine learning framework, including CTSH (men), and TNFRSF4 (both sexes). CONCLUSIONS: We identified sex-specific associations of proteins and biological pathways with incident CAD. Whereas the majority of proteins had consistent associations in both men and women, our findings suggest a degree of sex-specific pathogenesis with evidence for potential causality, opening new alleys for tailored prevention strategies and clinical cardiovascular risk management.

Journal Article↗
PubMed2006

Vascular remodeling and protease inhibition--bench to bedside.

Physiological and pathological tissue remodeling needs an orderly degradation of the extracellular matrix. Matrix metalloproteinases (MMPs) are proteases capable of degrading different extracellular matrix components, including collagen and elastin. MMP expression is strongly enhanced in vascular pathologies such as stenosis following balloon dilation, in-stent restenosis, sustained flow changes, aneurysm formation, and atherosclerosis. Experimental studies have revealed that some biological actions of MMPs aggravate a pathological condition, whereas others may be beneficial for the patient suffering from atherosclerotic disease. Therefore, a better understanding of the biological consequence and regulation of MMP activity is critical for the design and potential application of specific MMP inhibitors in vascular disease. In this review, we will give an overview of preclinical experimental studies using MMP inhibitors with the objective to influence vascular occlusive diseases, and we will also highlight new targets that influence MMP expression and activity and that possess potential for therapeutic interventions.

Adaptation, Physiological↗
PubMed2006

Pharmaceutical interventions to influence arteriogenesis: new concepts to treat ischemic heart disease.

Despite the technical progress in interventional techniques to overcome the harmful effects of ischemic heart disease there is still an urgent need for alternative, pharmaceutical treatment modalities. Exogenous stimulation of vessel growth, i.e. vasculogenesis, angiogenesis or arteriogenesis serves as a promising strategy to restore blood flow to the jeopardized tissue regions downstream of arterial stenosis or occlusion. While vasculogenesis is defined as the arrangement of angioblasts during prenatal development creating the first vascular network, angiogenesis and arteriogenesis refer to important adaptive mechanisms in the adult organism. Angiogenesis, neo-formation of capillaries, is a key process in many different physiological and pathophysiological events where improvement of microvascular function and tissue nutrition is needed (e.g. wound healing, tumor growth). In contrast to this capillary sprouting, the term arteriogenesis refers to the development of large caliber collateral arteries. Under conditions of increasing shear stress, anastomoses between interconnected perfusion territories can undergo adaptive enlargement, developing into a functional network of collateral arteries, natural bypasses able to maintain sufficient blood flow and compensating for the gradual occlusion of a large artery (e.g. in the coronary circulation). However, in most cases arteriogenesis does not proceed as fast as the stenosis progresses and infarction and tissue necrosis results. A well-developed collateral network is an important protective factor for the occurrence of ischemic events and therefore pharmaceutical acceleration and stimulation of arteriogenesis in patients represents an eminent aim for the future. This review focuses on the basic mechanisms of arteriogenesis, the recent progresses in translating these insights into the clinical situation and the problems yet to be solved.

Angiogenesis Inducing Agents↗
PubMed2005

Matrix metalloproteinase 2 is associated with stable and matrix metalloproteinases 8 and 9 with vulnerable carotid atherosclerotic lesions: a study in human endarterectomy specimen pointing to a role for different extracellular matrix metalloproteinase inducer glycosylation forms.

BACKGROUND AND PURPOSE: We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics. METHODS: Carotid atherosclerotic plaques (n=150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and macrophages. Adjacent segments were used to isolate total protein to assess MMP-2 and MMP-9 activities and gelatin breakdown, MMP-8 activity, and EMMPRIN levels. RESULTS: Macrophage-rich lesions revealed higher MMP-8 and MMP-9 activities, whereas SMC-rich lesions showed higher MMP-2 activity. The levels of less glycosylated EMMPRIN-45kD were higher in SMC-rich lesions and lower in macrophage-rich plaques. EMMPRIN-45kD was associated with MMP-2 levels, whereas EMMPRIN-58kD was related to MMP-9 levels. CONCLUSIONS: MMP-2, MMP-8, and MMP-9 activities differed among carotid plaque phenotypes. Different EMMPRIN glycosylation forms are associated with either MMP-2 or MMP-9 activity, which suggests that EMMPRIN glycosylation may play a role in MMP regulation and plaque destabilization.

Analysis of Variance↗
PubMed2005

Involvement of furin-like proprotein convertases in the arterial response to injury.

BACKGROUND: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been studied yet. We studied furin, MT1-MMP, MMP levels and TGF-beta signaling after arterial injury. We also investigated the effect of an inhibitor of furin-like PCs, alpha1-antitrypsin Portland (alpha1-PDX), on arterial injury following balloon dilation. METHODS AND RESULTS: NZW rabbit femoral and iliac arteries (N=42) were balloon dilated unilaterally and harvested after 2, 7, 14, 28 or 42 days. Furin mRNA levels were increased after 2 and 7 days. MMP-2 and MT1-MMP levels were increased after day 7 and TGF-beta signaling, by phosphorylating Smad 1/5 and 2/3, was increased at all time points. Inhibition of furin-like PCs, by adenoviral over-expression of alpha1-PDX, blocked proTGF-beta activation and Smad phosphorylation, and reduced MT1-MMP and MMP-2 activation (N=5). In vivo adventitial inhibition of furin-like PCs (N=9) resulted in a reduction of 13.1+/-5.2% in advential and 23.6+/-7.9% in intimal areas (P<0.05), but had no effect on lumen size due to decreased vessel areas. CONCLUSIONS: This study demonstrates that furin-like PCs are involved in the arterial response to injury possibly through activation of the TGF-beta-Smad signaling pathway and identifies furin-like PCs as a possible target to inhibit intimal hyperplasia.

Adenoviridae↗
PubMed2005

In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity.

AIMS: Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. METHODS AND RESULTS: Plaques were experimentally induced in rabbit (n=11) aortas, and at the day of sacrifice, a pull-back was performed with a thermography catheter. Hot (n=10), cold (n=10), and reference (n=11) regions were dissected and analysed for smooth muscle cell (SMC), lipids (L), collagen (COL), and macrophage (MPhi) cell densities (%); a vulnerability index (VI) was calculated as VI=MPhi+L/(SMC+COL). In addition, accumulation and activity of MMP-2 and MMP-9 were determined with zymography. Ten hot regions were identified with an average temperature of 0.40+/-0.03 degrees C (P<0.05 vs. reference) and 10 cold regions with 0.07+/-0.03 degrees C (P<0.05 vs. hot). In the hot regions, a higher macrophage density (173%), less SMC density (77%), and a higher VI (100%) were identified. In addition, MMP-9 (673%) activity was increased. A detailed regression analysis revealed that MMP-9 predicted hot regions better than macrophage accumulation alone. CONCLUSION: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.

Animals↗
PubMed2005

In vivo cell seeding with anti-CD34 antibodies successfully accelerates endothelialization but stimulates intimal hyperplasia in porcine arteriovenous expanded polytetrafluoroethylene grafts.

BACKGROUND: The patency of AV expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. The absence of a functional endothelial monolayer on the prosthetic grafts is an important stimulus for IH. In the present study, we evaluated the feasibility of capturing endothelial progenitor cells in vivo using anti-CD34 antibodies on ePTFE grafts to inhibit IH in porcine AV ePTFE grafts. METHODS AND RESULTS: In 11 pigs, anti-CD34-coated ePTFE grafts were implanted between the carotid artery and internal jugular vein. Bare ePTFE grafts were implanted at the contralateral side. After 3 (n=2) or 28 (n=9) days, the pigs were terminated, and the AV grafts were excised for histological analysis and SEM. At 3 and 28 days after implantation, 95% and 85% of the coated graft surface was covered by endothelial cells. In contrast, no cell coverage was observed in the bare graft at 3 days, whereas at 28 days, bare grafts were partly covered with endothelial cells (32%; P=0.04). Twenty-eight days after implantation, IH at the venous anastomosis was strongly increased in anti-CD34-coated grafts (5.96+/-1.9 mm2) compared with bare grafts (1.70+/-0.4 mm2; P=0.03). This increase in IH coincided with enhanced cellular proliferation at the venous anastomosis. CONCLUSIONS: Autoseeding with anti-CD34 antibodies results in rapid endothelialization within 72 hours. Despite persistent endothelial graft coverage, IH at the outflow tract is increased profoundly at 4 weeks after implantation. Further modifications are required to stimulate the protective effects of trapped endothelial cells.

Animals↗
PubMed2005

Sirolimus-eluting stents to abolish intimal hyperplasia and improve flow in porcine arteriovenous grafts: a 4-week follow-up study.

BACKGROUND: The patency of arteriovenous (AV) expanded polytetrafluoroethylene (ePTFE) hemodialysis grafts is severely compromised by intimal hyperplasia (IH) at the venous anastomosis and in the venous outflow tract. We addressed the potential of primary placement of a sirolimus-eluting stent (SES) in a validated porcine model. METHODS AND RESULTS: In 25 pigs, ePTFE AV grafts were created bilaterally between the carotid artery and the jugular vein, whereupon a self-expandable nitinol stent (14 SESs and 11 bare-metal stents) was implanted over the venous anastomosis in 1 of the 2 grafts. After exclusion of technical failures and 1 unilateral occlusion, 16 pigs (9 SESs and 7 bare-metal stents) were included for further analysis. After 28 days, we measured graft flow and performed quantitative angiography. The pigs were then euthanized, and grafts with adjacent vessels were excised for histological analysis. Minimal luminal diameter was substantially larger in the SES group compared with unstented controls (5.9+/-0.2 versus 3.8+/-0.4 mm, respectively, P=0.01), which was accompanied by more prominent graft flow (SES, 1360+/-89 mL/min versus unstented, 861+/-83 mL/min, P=0.05). IH at the venous anastomosis was 77% less in the SES group compared with unstented controls (0.44+/-0.05 versus 1.92+/-0.5 mm2, respectively, P=0.01), whereas IH increased markedly when bare-metal stents were used (5.7+/-1.4 mm2, P=0.05). CONCLUSIONS: SESs in the venous outflow of AV grafts significantly reduce IH and increase vessel diameter and graft flow compared with unstented grafts. These findings suggest that SESs have the potential to improve primary patency of AV grafts in hemodialysis patients.

Animals↗
PubMed2005

Impact of different definitions on the interpretation of coronary remodeling determined by intravascular ultrasound.

The objective of this study was to compare the categorizations and determinants related to remodeling by the three definitions commonly used. Several morphological and intravascular ultrasound (IVUS) studies have demonstrated the fundamental importance of arterial remodeling in atherosclerosis. However, lack of consensus on how to define remodeling has led to conflicting analyses of factors that influence this process. Analysis of pre-interventional IVUS images of 514 lesions in native coronary arteries was performed. Arterial remodeling was defined as outward by definition 1, when [cross-sectional area (CSA) of the external elastic membrane (EEM) at the lesion site (EEM(lesion))]/[EEM CSA either at the proximal (EEM(prox ref)) or distal (EEM(distal ref)) reference site with the least amount of plaque] was > 1.05, intermediate when this ratio was between 0.95 and 1.05, and inward when < 0.95. Remodeling was defined as outward by definition 2 when EEM(lesion) > both EEM(prox ref) and EEM(distal ref), inward when EEM(lesion) < both EEM(prox ref) and EEM(distal ref), and intermediate when EEM(lesion) was intermediate between EEM(prox ref) and EEM(distal ref). By definition 3, vessel remodeling was defined as outward when EEM(lesion) > (EEM(prox ref) + EEM(distal ref))/2 and intermediate/inward when EEM(lesion) < or = (EEM(prox ref) + EEM(distal ref))/2. The frequency of outward remodeling was significantly higher by definitions 1 and 3 than by definition 2, whereas a higher frequency of inward remodeling was observed in definition 1, resulting in significantly different remodeling distributions between the three definitions (P < 0.0001). By multivariate logistic analysis, the only clinical determinants related to outward remodeling was younger age, and only by definition 3. IVUS determinants varied significantly between the three definitions. The only consistent determinants among the three definitions were smaller lumen CSA at the reference site and larger plaque + media CSA at the lesion site. This study demonstrates the significant impact of different remodeling definitions on the incidence and determinants of remodeling patterns. The marked variability in categorization of remodeling underscores the importance of developing a standard methodology.

Aged↗
PubMed2005

Carotid atherosclerotic plaques in patients with transient ischemic attacks and stroke have unstable characteristics compared with plaques in asymptomatic and amaurosis fugax patients.

INTRODUCTION: Atherosclerotic carotid artery disease is responsible for a variety of clinical presentations, ranging from asymptomatic to cerebral ischemic events. Considering the upcoming use of noninvasive imaging modalities, plaque characteristics could serve as a marker in the selection of patients eligible for carotid endarterectomy (CEA). This would be more likely if characteristics corresponded with clinical manifestations and were predictive of future events. In this study, we hypothesized that plaque characteristics correlate with the clinical presentation of carotid artery disease. METHODS: We included 404 patients undergoing a carotid endarterectomy (CEA). Ipsilateral clinical symptoms and duplex measurements were recorded. Patients could be asymptomatic (23.5%) or symptomatic with stroke (26.5%), transient ischemic attack (TIA) (36.1%), or amaurosis fugax (AFX) (13.9%). Plaques were stained and semi-quantitatively analyzed for the presence of macrophages, smooth muscle cells, collagen, calcifications, and thrombus. Plaques were categorized in three phenotypes by their overall presentation and the amount of fat. In addition, plaque matrix metalloproteinase (MMP) activity and cytokines expressions were measured. RESULTS: Fibrous, fibro-atheromatous, and atheromatous plaques were observed in 30.2%, 35.6%, and 34.2%, respectively. Atheromatous plaques were more prevalent in patients with stroke and TIA compared with asymptomatic patients or patients with AFX (P = .001). Collagen staining was less evident in patients with TIA and stroke compared with asymptomatic patients or patients with AFX (P < .001). Plaques of patients with TIA and stroke showed significantly higher activity levels of MMP-8 and MMP-9 and higher levels of interleukin-8 compared with asymptomatic and AFX patients. CONCLUSION: Plaque phenotype of patients with TIA is comparable to that of patients with stroke; whereas, the plaque phenotype of patients with AFX resembles the plaque phenotype of asymptomatic patients. Follow-up studies should be encouraged to determine whether plaque characteristics visualized by imaging techniques might help to identify patients most likely to benefit from CEA.

Aged↗
PubMed2005

Closure of the arteriotomy after carotid endarterectomy: patch type is related to intraoperative microemboli and restenosis rate.

OBJECTIVE: Patch closure after carotid endarterectomy (CEA) improves clinical outcome compared with primary closure. Whether there are differences in outcome between various patch materials is still not clear. The objective of this retrospective study was to investigate whether a relationship exists between the patch type and the number of microemboli as registered during CEA by transcranial Doppler imaging, the clinical outcome (transient ischemic attack and cerebrovascular accident), and the occurrence of restenosis. METHODS: We included 319 patients who underwent CEA. Intraoperative microembolus registration was performed in 205 procedures. Microembolization was recorded during four different periods: dissection, shunting, clamp release, and wound closure. The decision to perform primary closure or to use a patch for the closure of the arteriotomy was made by the surgeon, and Dacron patches were used when venous material was insufficient. Cerebral events were recorded within the first month after CEA, and duplex scanning was performed at 3 months (n = 319) and 1 year (n = 166) after CEA. A diameter reduction of more than 70% was defined as restenosis. RESULTS: Primary, venous, and Dacron patch closures were performed in 83 (26.0%), 171 (53.6%), and 65 (20.4%) patients, respectively. Primary closure was significantly related to sex (Dacron patch, 35 men and 30 women; venous patch, 108 men and 63 women; primary closure, 72 men and 11 women; P < .001). The occurrence of microemboli during wound closure was also related to sex (women, 2.5 +/- 0.6; men, 1.0 +/- 0.2; P = .01). Additionally, during clamp release, Dacron patches were associated with significantly more microemboli than venous patches (11.1 +/- 3.4 vs 4.0 +/- 0.9; P < .01), and this difference was also noted during wound closure (3.1 +/- 0.9 vs 1.4 +/- 0.4; P < .05). Transient ischemic attacks and minor strokes after CEA occurred in 5 (2.4%) of 205 and 6 (2.9%) of 205 procedures, respectively, and the degree of microembolization during dissection was related to adverse cerebral events (P = .003). In contrast, the type of closure was not related to immediate clinical adverse events. However, primary closure and Dacron patches were associated with an increase in the restenosis rate compared with venous patches: after 400 days, the restenosis rate for Primary closure was 11%, Dacron patch 16%, and venous patch 7% (P = .05; Kaplan-Meier estimates). CONCLUSIONS: Microemboli are more prevalent during clamp releases and wound closure when Dacron patches are used. Additionally, the observed differences in embolization noted by patch type were mainly evident in women. However, the use of Dacron patches was not related to immediate ischemic cerebral events but was associated with a higher restenosis rate compared with venous patch closure. This suggests that venous patch closure may be preferred for CEA.

Adult↗
PubMed2005

Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography.

Optical coherence tomography (OCT) is a novel, high-resolution diagnostic tool that is capable of imaging the arterial wall and plaques. The differentiation between different types of atherosclerotic plaque is based on qualitative differences in gray levels and structural appearance. We hypothesize that a quantitative data analysis of the OCT signal allows measurement of light attenuation by the local tissue components, which can facilitate quantitative spatial discrimination between plaque constituents. High-resolution OCT images (at 800 nm) of human atherosclerotic arterial segments obtained at autopsy were histologically validated. Using a new, simple analysis algorithm, which incorporates the confocal properties of the OCT system, the light attenuation coefficients for these constituents were determined: for diffuse intimal thickening (5.5 +/- 1.2 mm(-1)) and lipid-rich regions (3.2 +/- 1.1 mm(-1)), the attenuation differed significantly from media (9.9 +/- 1.8 mm(-1)), calcifications (11.1 +/- 4.9 mm(-1) ) and thrombi (11.2 +/- 2.3 mm(-1)) (p < 0.01). These proof of principle studies show that simple quantitative analysis of the OCT signals allows spatial determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest. Combining morphological imaging by OCT with the observed differences in optical attenuation coefficients of the various regions may enhance discrimination between various plaque types.

Algorithms↗
PubMed2004

Increase in collagen turnover but not in collagen fiber content is associated with flow-induced arterial remodeling.

BACKGROUND: Degradation and synthesis of collagen are common features in arterial geometrical remodeling. Previous studies described an association between arterial remodeling and an increase in collagen fiber content after balloon injury. However, this does not exclude that the association between collagen content and remodeling depends on arterial injury since the association of collagen fiber content and arterial remodeling, without arterial injury, has not been investigated. The aim of the present study was to study the relation between flow-induced arterial geometrical remodeling, without arterial injury, and collagen synthesis and degradation, collagen fiber content and cell-migration-associated moesin levels. METHODS AND RESULTS: In 23 New Zealand White rabbits an arteriovenous shunt (AV shunt) was created in the carotid and femoral artery to induce a structural diameter increase or a partial ligation (n = 27 rabbits) to induce a diameter decrease. In both models, arterial remodeling was accompanied by increased procollagen synthesis, reflected by increased procollagen mRNA or Hsp47 protein levels. In both models, however, no changes were detected in collagen fiber content. Active MMP-2 and moesin levels were increased after AV shunting. CONCLUSIONS: Collagen synthesis and MMP-2 activation were associated with arterial remodeling. However, a change in collagen fiber content was not observed. These results suggest that, during flow-induced geometrical arterial remodeling, increases in collagen synthesis are used for matrix collagen turnover and cell migration but not to augment collagen fiber content.

Animals↗
PubMed2004

Vascular remodeling in atherosclerotic femoral arteries: three-dimensional US analysis.

PURPOSE: To investigate the various modes of vascular remodeling of atherosclerotic femoral arteries and determine the associations between type of arterial remodeling and clinical data (age, sex, and medical history) and inflammatory parameters. MATERIALS AND METHODS: Intravascular ultrasonography (US) of the femoral arteries was performed in 50 patients with clinical symptoms of peripheral vascular disease. To determine the arterial remodeling mode (expansive remodeling [ER], involving compensatory enlargement of the artery, or constrictive remodeling [CR], involving vessel constriction during progression of atherosclerosis), the cross-sectional areas (CSAs) of the external elastic membrane (EEM), lumen, and plaque-plus-media were measured every 0.1 mm by using three-dimensional reconstruction. Clinical, laboratory, and intravascular US data were compared in the different remodeling groups (dominant ER, dominant CR, or mixed remodeling) by using analysis of variance supplemented by Tukey-Kramer tests. Multivariate analysis was performed to test independent variables predicting dominant ER. RESULTS: Intravascular US revealed the parallel existence of ER and CR in all patients: Increases and decreases in EEM in response to plaque growth could be observed within the same artery. ER dominated in 13 (26%) patients, and CR dominated in 11 (22%) patients: At least 80% of EEM CSAs were higher or lower than the mean of the EEM CSAs of the segments proximal and distal to the lesion. Patients with dominant ER had higher levels of serum C-reactive protein (CRP) compared with levels in patients with dominant CR and patients with mixed remodeling (1.62 mg/dL +/- 2.05 [standard deviation] vs 0.19 mg/dL +/- 0.33 and 0.21 mg/dL +/- 0.39, respectively, P < .005). Multivariate analysis revealed high CRP level to be a significant independent predictor for dominant ER (P < .01). CONCLUSION: The parallel existence of ER and CR was found in all patients with peripheral atherosclerosis, with a dominance of vessel expansion in 26% of patients. Higher plasma CRP level was associated with dominant ER.

Aged↗
PubMed2004

Expansive arterial remodeling: location, location, location.

The artery is a dynamic organ capable of changing its geometry in response to atherosclerotic plaque formation. Expansion of the vessel diameter retards luminal narrowing and is considered a compensatory response. However, the expansive remodeling response is a "wolf in sheep's clothes," because expansion is associated with the presence of inflammatory cells, proteolysis, and a thrombotic plaque phenotype. The prevalence and clinical presentation of expansively remodeled lesions may differ among vascular beds. However, it is evident that all types of atherosclerotic arterial expansive lesions share the presence of inflammatory cells and subsequent protease activities. The potential role of inflammation and protease activity in the development of the different remodeling modes is discussed.

Adaptation, Physiological↗
PubMed2004

Increased collagen turnover is only partly associated with collagen fiber deposition in the arterial response to injury.

OBJECTIVE: In the arterial response to injury, collagen breakdown has been studied extensively, but little is known on collagen synthesis and fiber formation. Here, we studied in vivo collagen synthesis and collagen fiber content in relation to collagen breakdown following arterial balloon injury. METHODS AND RESULTS: Twenty-five New Zealand White rabbits were balloon dilated in femoral and iliac arteries and terminated at 2, 7, 14 and 28 days. From day 7, both constrictive arterial remodeling and intimal hyperplasia were observed. Collagen degradation, synthesis and fiber content were studied using zymography, quantitative Polymerase Chain Reaction, Western blotting and picrosirius red staining. Collagen synthesis, reflected by procollagen I and heat shock protein 47 (Hsp47) expression, increased at day 2 with a maximum at day 14 and was accompanied by increased collagen breakdown as reflected by matrix metalloproteinase-1 and -2 levels. Collagen content in media and adventitia only increased between days 2 and 7 after balloon injury. CONCLUSIONS: In the first week after arterial injury, increased collagen content is associated with increased collagen synthesis and degradation. However, after 1 week, collagen turnover remains high in contrast to increased collagen fiber content. This suggests that after 1 week, collagen turnover is used for other processes like cell migration and arterial remodeling.

Angioplasty, Balloon↗