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Mat J A P Daemen

Publications and source records attributed to Mat J A P Daemen.

At least 19 recordsLinked to original sources
PubMed2006

Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress.

BACKGROUND: Atherosclerotic lesions are predominantly observed in curved arteries and near side branches, where low or oscillatory shear stress patterns occur, suggesting a causal connection. However, the effect of shear stress on plaque vulnerability is unknown because the lack of an appropriate in vivo model precludes cause-effect studies. METHODS AND RESULTS: We developed a perivascular shear stress modifier that induces regions of lowered, increased, and lowered/oscillatory (ie, with vortices) shear stresses in mouse carotid arteries and studied plaque formation and composition. Atherosclerotic lesions developed invariably in the regions with lowered shear stress or vortices, whereas the regions of increased shear stress were protected. Lowered shear stress lesions were larger (intima/media, 1.38+/-0.68 versus 0.22+/-0.04); contained fewer smooth muscle cells (1.9+/-1.6% versus 26.3+/-9.7%), less collagen (15.3+/-1.0% versus 22.2+/-1.0%), and more lipids (15.8+/-0.9% versus 10.2+/-0.5%); and showed more outward vascular remodeling (214+/-19% versus 117+/-9%) than did oscillatory shear stress lesions. Expression of proatherogenic inflammatory mediators and matrix metalloproteinase activity was higher in the lowered shear stress regions. Spontaneous and angiotensin II-induced intraplaque hemorrhages occurred in the lowered shear stress regions only. CONCLUSIONS: Lowered shear stress and oscillatory shear stress are both essential conditions in plaque formation. Lowered shear stress induces larger lesions with a vulnerable plaque phenotype, whereas vortices with oscillatory shear stress induce stable lesions.

Angiotensin II↗
PubMed2006

Drug-eluting stents studies in mice: do we need atherosclerosis to study restenosis?

In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical trials with disappointing outcomes. Little is known concerning potential adverse effects on vessel wall integrity and (re)healing, atherosclerotic lesion formation, progression, and plaque stability of these DES. Although efficacy and safety need to be determined clinically, preclinical testing of candidate drugs in well-defined animal models is extremely helpful to gain insight into the basic biological responses to candidate compounds. Here, we discuss and report an animal model which enables rapid screening of candidate drugs for DES on an atherosclerotic background. The results from drug testing using this novel model could help to quickly and cost-effectively establish the dose range of candidate drugs with reasonable potential for DES.

Animals↗
PubMed2005

Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: validation using a novel monocyte chemoattractant protein monoclonal antibody.

BACKGROUND: Pathological aspects of atherosclerosis are well described, but gene profiles during atherosclerotic plaque progression are largely unidentified. METHODS AND RESULTS: Microarray analysis was performed on mRNA of aortic arches of ApoE-/- mice fed normal chow (NC group) or Western-type diet (WD group) for 3, 4.5, and 6 months. Of 10 176 reporters, 387 were differentially (>2x) expressed in at least 1 group compared with a common reference (ApoE-/-, 3- month NC group). The number of differentially expressed genes increased during plaque progression. Time-related expression clustering and functional grouping of differentially expressed genes suggested important functions for genes involved in inflammation (especially the small inducible cytokines monocyte chemoattractant protein [MCP]-1, MCP-5, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, MIP-2, and fractalkine) and matrix degradation (cathepsin-S, matrix metalloproteinase-2/12). Validation experiments focused on the gene cluster of small inducible cytokines. Real-time polymerase chain reaction revealed a plaque progression-dependent increase in mRNA levels of MCP-1, MCP-5, MIP-1alpha, and MIP-1beta. ELISA for MCP-1 and MCP-5 showed similar results. Immunohistochemistry for MCP-1, MCP-5, and MIP-1alpha located their expression to plaque macrophages. An inhibiting antibody for MCP-1 and MCP-5 (11K2) was designed and administered to ApoE-/- mice for 12 weeks starting at the age of 5 or 17 weeks. 11K2 treatment reduced plaque area and macrophage and CD45+ cell content and increased collagen content, thereby inducing a stable plaque phenotype. CONCLUSIONS: Gene profiling of atherosclerotic plaque progression in ApoE-/- mice revealed upregulation of the gene cluster of small inducible cytokines. Further expression and in vivo validation studies showed that this gene cluster mediates plaque progression and stability.

Animals↗
PubMed2005

Polycyclic aromatic hydrocarbons induce an inflammatory atherosclerotic plaque phenotype irrespective of their DNA binding properties.

Although it has been demonstrated that carcinogenic environmental polycyclic aromatic hydrocarbons (PAHs) cause progression of atherosclerosis, the underlying mechanism remains unclear. In the present study, we aimed to investigate whether DNA binding events are critically involved in the progression of PAH-mediated atherogenesis. Apolipoprotein E knockout mice were orally (24 wk, once/wk) exposed to 5 mg/kg benzo[a]pyrene (B[a]P), or its nonmutagenic, noncarcinogenic structural isoform benzo[e]pyrene (B[e]P). 32P-postlabeling of lung tissue confirmed the presence of promutagenic PAH-DNA adducts in B[a]P-exposed animals, whereas in B[e]P-exposed and vehicle control animals, these adducts were undetectable. Morphometrical analysis showed that both B[a]P and B[e]P caused an increase in plaque size, whereas location or number of plaques was unaffected. Immunohistochemistry revealed no differences in oxidative DNA damage (8-OHdG) or apoptosis in the plaques. Also plasma lipoprotein levels remained unchanged after PAH-exposure. However, T lymphocytes were increased > or =2-fold in the plaques of B[a]P- and B[e]P-exposed animals. Additionally, B[a]P and to a lesser extent B[e]P exposure resulted in increased TGFbeta protein levels in the plaques, that was mainly localized in the plaque macrophages. In vitro studies using the murine macrophage like RAW264.7 cells showed that inhibition of TGFbeta resulted in decreased tumor necrosis factor (TNF) alpha release, suggesting that enhanced TGFbeta expression in the plaque macrophages contributes to the proinflammatory effects in the vessel wall. In general, this inflammatory reaction in the plaques appeared to be a local response since peripheral blood cell composition (T cells, B cells, granulocytes, and macrophages) was not changed upon PAH exposure. In conclusion, we showed that both B[a]P and B[e]P cause progression of atherosclerosis, irrespective of their DNA binding properties. Moreover, our data revealed a possible novel mechanism of PAH-mediated atherogenesis, which likely involves a TGFbeta-mediated local inflammatory reaction in the vessel wall.

Animals↗
PubMed2005

Proteomic analysis of differential protein expression in human atherosclerotic plaque progression.

In this study, differential protein expression was assessed during human atherosclerotic plaque progression. A multifaceted approach was used in which differential protein expression was studied by two-dimensional (2D) gel electrophoresis and validated in individual patients using western blotting and immunohistochemistry. 2D profiles of whole-mount advanced stable lesions were compared to those of plaques containing a thrombus. Mass spectrometry analysis identified vinexin-beta and alpha1-antitrypsin (AAT) in the same spot that was differentially expressed in plaques with a thrombus. Immunohistochemistry and western blotting showed limited expression of both vinexin-beta and AAT in early lesions, whereas high expression of both proteins was found in advanced lesions. Differential expression of vinexin-beta in lesions with a thrombus compared to stable plaques could not be confirmed, indicating the importance of validation of proteomic analysis. For AAT, western blotting of 2D gels revealed expression of six isoforms in advanced plaques, one of which was confirmed to be solely expressed in thrombus-containing plaques. In conclusion, vinexin-beta is expressed in advanced human atherosclerotic plaques, but differential expression of this protein in lesions with a thrombus versus stable plaques could not be confirmed. However, this analysis revealed expression of six isoforms of AAT in advanced plaques, one of which was uniquely expressed in thrombus-containing plaques.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Low-dose FK506 blocks collar-induced atherosclerotic plaque development and stabilizes plaques in ApoE-/- mice.

Since atherosclerosis is a chronic inflammatory disease, we tested the hypothesis that the immunosuppressive drug FK506 would attenuate the development of atherosclerosis using a mouse model of collar-induced atherosclerosis. ApoE-/- mice were treated for 4 weeks with the immunosuppressive drug FK506 (0.05 mg/kg/day), yielding sustained blood levels (approximately 0.2 ng/mL) without systemic side effects. Atherosclerotic plaque development of FK506-treated mice was significantly reduced (63%) while plaque cell density was increased (52%) compared to controls. Importantly, FK506 also blocked progression of pre-existing atherosclerotic plaques. Plaque area of pre-existing plaques was 35% reduced by FK506. Cell density (35%) and collagen content (51%) were significantly increased, whereas necrotic core content was decreased (42%), indicating a more stable plaque morphology. Similar results were found during spontaneous atherosclerotic plaque development in ApoE-/- mice (treatment 17-25 weeks of age). Flow-cytometric analysis showed no peripheral effects on blood cell count or T-cell activation after FK506-treatment. In vitro, FK506 decreased vascular smooth muscle cell (VSMC) apoptosis and inhibited nuclear factor of activated T cells (NFAT)-luciferase reporter activity at concentrations in the range of the in vivo concentration. Low-dose FK506 inhibits collar-induced atherosclerotic plaque development and progression and induces more stable plaque phenotypes in ApoE-/- mice without any peripheral side effects.

Animals↗
PubMed2005

Assessment of human atherosclerotic carotid plaque components with multisequence MR imaging: initial experience.

PURPOSE: To prospectively determine, by using a stepwise logistic regression model, the optimal magnetic resonance (MR) weighting (ie, pulse sequence) combinations for plaque assessment and corresponding cutoff values of relative signal intensities (rSIs). MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained. Eleven patients (seven men, four women; mean age +/- standard deviation, 68 years +/- 4) with symptomatic carotid disease and stenosis of more than 70% were investigated at MR imaging before carotid endarterectomy. The MR images were matched with histologic features of the endarterectomy specimens (reference standard). The rSIs (compared with that of muscle tissue) from regions of interest were assessed qualitatively and semiquantitatively. For all major components (calcification, lipid core, intraplaque hemorrhage, and fibrous tissue), optimal cutoff points for the rSIs were determined for five MR weightings by means of receiver operating characteristic curves. The best predicting combinations of these five dichotomized MR weightings were selected by means of stepwise logistic regression analysis. The potential sensitivity and specificity of MR imaging for vulnerable plaque with hemorrhage and/or lipid core were determined. RESULTS: The same optimal MR weighting combinations for identifying the four plaque components were found with qualitative and semiquantitative analysis. Sensitivity and specificity for vulnerable plaque were 93% (95% confidence interval: 77%, 99%) and 96% (95% confidence interval: 86%, 100%), respectively, for the qualitative analysis and 76% (95% confidence interval: 56%, 90%) and 100% (95% confidence interval: 93%, 100%) for the semiquantitative analysis. CONCLUSION: This study demonstrates the potential of a systematic approach of atherosclerotic plaque assessment with multisequence MR imaging by using the information provided from five different MR weightings in a stepwise logistic regression model.

Aged↗
PubMed2004

Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis.

BACKGROUND: Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis. METHODS AND RESULTS: To assess the role of IL-6 in atherosclerosis, ApoE-/--IL-6-/- double-knockout mice were generated, fed a normal chow diet, and housed for 53+/-4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE-/--IL-6-/- mice compared with ApoE-/-, wild-type (WT), and IL-6-/- mice. Plaques of ApoE-/--IL-6-/- mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE-/--IL-6-/- mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced. CONCLUSIONS: Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoEK-/--IL-6-/- mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.

Animals↗
PubMed2004

Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism.

OBJECTIVES: We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion. BACKGROUND: The FGFs display cardioprotective effects during ischemia and reperfusion. METHODS: We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular signaling pathways responsible for these effects in an ex vivo murine setup of myocardial ischemia and reperfusion. RESULTS: Cardiac-specific human FGF-1 overexpression was associated with enhanced post-ischemic hemodynamic recovery and decreased lactate dehydrogenase release during reperfusion. Inhibition of the FGF receptor, protein kinase C (PKC), and tyrosine kinase (TK) resulted in blockade of FGF-1-induced protective effects on cardiac functional recovery and cell death. CONCLUSIONS: The overexpression of FGF-1 induces cardioprotection through a pathway that involves the FGF receptor, PKC, and TK.

Animals↗
PubMed2004

Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy.

Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting molecular prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray analysis to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.19+/-0.01) versus normal ejection fraction (0.11+/-0.03 [arbitrary units]; P<0.05). Angiotensin II induced fatal cardiac rupture in 70% of TSP2 knockout mice, with cardiac failure in the surviving mice; this was not seen in wild-type mice. In TSP2 knockout mice, angiotensin II increased matrix metalloproteinase (MMP)-2 and MMP-9 activity by 120% and 390% compared with wild-type mice (P<0.05). In conclusion, we identify TSP2 as a crucial regulator of the integrity of the cardiac matrix that is necessary for the myocardium to cope with increased loading and that may function by its regulation of MMP activity. This suggests that expression of TSP2 marks an early-stage molecular program that is activated uniquely in hypertrophied hearts that are prone to fail.

Angiotensin II↗
PubMed2004

In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging.

PURPOSE: To investigate the performance of high-resolution T1-weighted (T1w) turbo field echo (TFE) magnetic resonance imaging (MRI) for the identification of the high-risk component intraplaque hemorrhage, which is described in the literature as a troublesome component to detect. MATERIALS AND METHODS: An MRI scan was performed preoperatively on 11 patients who underwent carotid endarterectomy because of symptomatic carotid disease with a stenosis larger than 70%. A commonly used double inversion recovery (DIR) T1w turbo spin echo (TSE) served as the T1w control for the T1w TFE pulse sequence. The MR images were matched slice by slice with histology, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the MR images were calculated. Additionally, two readers, who were blinded for the histological results, independently assessed the MR slices concerning the presence of intraplaque hemorrhage. RESULTS: More than 80% of the histological proven intraplaque hemorrhage could be detected using the TFE sequence with a high interobserver agreement (Kappa = 0.73). The TFE sequence proved to be superior to the TSE sequence concerning SNR and CNR, but also in the qualitative detection of intraplaque hemorrhage. The false positive TFE results contained fibrous tissue and were all located outside the main plaque area. CONCLUSION: The present study shows that in vivo high-resolution T1w TFE MRI can identify the high-risk component intraplaque hemorrhage with a high detection rate in patients with symptomatic carotid disease. Larger clinical trials are warranted to investigate whether this technique can identify patients at risk for an ischemic attack.

Aged↗
PubMed2004

Chronic exposure to the carcinogenic compound benzo[a]pyrene induces larger and phenotypically different atherosclerotic plaques in ApoE-knockout mice.

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon with atherogenic and carcinogenic properties. The role of B[a]P in carcinogenesis is well established, and thought to exert via enzymatic activation into reactive metabolites that are capable of binding to the DNA leading to uncontrolled proliferation. However, the mechanism underlying the atherogenic properties of B[a]P is still unclear. Therefore, the effects of chronic B[a]P exposure on atherosclerotic plaque development in apolipoprotein E knockout (apoE-KO) mice were studied. ApoE-KO mice were orally treated with 5 mg/kg/bw B[a]P once per week for 12 or 24 consecutive weeks. Levels of reactive B[a]P metabolites in the arterial tree (from the aortic arch until the iliac artery bifurcations) were high as shown by the level of B[a]P DNA-binding products measured in DNA isolated from the entire aorta (38.9 +/- 4.8 adducts/10(8) nucleotides). Analysis of atherosclerotic lesions in the aortic arch showed no influence of B[a]P on location or number of lesions. Moreover, no increased levels of p53 nuclear protein accumulation or cell proliferation, as detected by immunohistochemistry, were seen in the plaques of the B[a]P-exposed animals. However, the effects of B[a]P on advanced lesions were obvious: advanced plaques were larger and more prone to lipid core development and plaque layering at both 12 and 24 weeks (P < 0.05). In the B[a]P-exposed animals advanced plaques contained more T-lymphocytes and macrophages than in the control animals at both end points (P < 0.05). These data suggest that B[a]P does not initiate atherosclerosis in apoE-KO mice, but accelerates the progression of atherosclerotic plaques via a local inflammatory response.

Animals↗
PubMed2003

Atherosclerotic plaque rupture: local or systemic process?

It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis. Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque fissuring, intraplaque hemorrhage, and erosion, are often used interchangeably. Moreover, the different phenotypes of the unstable plaque are mostly referred to as plaque rupture. In the first part of this review, we will focus on the definition of true plaque rupture and the definitions of other phenotypes of plaque instability, especially on intraplaque hemorrhage, and discuss the phenotypes of available animal models of plaque instability. The second part of this review will address the pathogenesis of plaque rupture from a local and a systemic perspective. Plaque rupture is thought to occur because of changes in the plaque itself or systemic changes in the patient. Interestingly, contributing factors seem to overlap to a great extent and might even be interrelated. Finally, we will propose an integrative view on the pathogenesis of plaque rupture.

Animals↗
PubMed2003

Serine protease inhibitor Serp-1 strongly impairs atherosclerotic lesion formation and induces a stable plaque phenotype in ApoE-/-mice.

The myxoma virus protein Serp-1 is a member of the serine protease inhibitor superfamily. Serp-1 potently inhibits human serum proteases including plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA). Serp-1 also displays a high antiinflammatory activity, rendering it a promising candidate for antiatherosclerotic therapy. In this study, we have thus examined the effect of Serp-1 on de novo atherosclerotic plaque formation and on advanced lesions. Perivascular collars were placed around carotid arteries of ApoE-/- mice to induce atherosclerotic plaques and Serp-1 treatment started at week 1 and week 5 after collar placement. Effects of Serp-1 on de novo atherogenesis were characterized by a significantly lower plaque size than that of control mice (18+/-5x10(3) versus 57+/-12x10(3) microm2, respectively; P=0.007). Immunostaining showed a 50% (P=0.004) decrease in the MOMA-2-stained lesion area of Serp-1-treated mice. Treatment of advanced lesions with Serp-1 resulted in a decrease in plaque size and lumen stenosis (P=0.028). Alpha-actin staining of these lesions was significantly increased compared with the control (P=0.017). In both studies, a higher cellularity of the plaque and increased collagen content was observed in Serp-1-treated mice. In vitro studies showed that Serp-1 induces proliferation and migration of vascular smooth muscle cells. In conclusion, Serp-1 inhibits carotid artery plaque growth and progression in ApoE-/- mice. Equally relevant, it enhances cellularity of the plaque core potentially leading to improved plaque stability. The above results indicate that Serp-1 constitutes a promising lead in antiatherosclerotic therapy.

Actins↗
PubMed2003

Vasculin, a novel vascular protein differentially expressed in human atherogenesis.

Recent suppressive subtractive hybridization analysis on human atherosclerotic plaque-derived RNA revealed genes upregulated in plaques with a thrombus versus stable plaques. Clone SSH6, containing part of a putative open reading frame of an unknown protein, was further investigated. Full-length cDNA, coding for a 473-amino acid (aa) protein, was identified in a vascular smooth muscle cell (SMC) cDNA library. Bioinformatics suggested the presence of multiple SSH6 variants due to alternative splicing of exon 3. Multiple-tissue Northern blot analysis demonstrated a differential expression pattern of these variants, as a ubiquitously expressed SSH6 mRNA missing exon 3, was detected apart from a putative vascular SMC-specific form containing exon 3. Western blot analysis indicated a ubiquitous 35-kDa protein (SSH6-beta), in addition to a 45-kDa protein (vasculin), detected in the vascular wall and in plasma. Analysis of arteries displaying various stages of atherosclerosis indicated that the vasculin/SSH6-beta ratio increases throughout atherogenesis. Immunohistochemical analysis demonstrated cytoplasmic expression of SSH6 gene products in macrophages, endothelial cells, and SMCs. In summary, we identified a novel mRNA/protein, vasculin, in the arterial wall and plasma. The regulated expression of vasculin in plaques suggests a role in atherogenesis. Moreover, its presence in plasma opens perspectives for vasculin as a marker for atherosclerosis.

Alternative Splicing↗
PubMed2003

Adjuvant cytokeratin staining in Mohs micrographic surgery for basal cell carcinoma.

BACKGROUND: Mohs micrographic surgery (MMS) is a technique that offers excellent cure rates in the treatment of basal cell carcinoma (BCC). One of the reasons for its success is the 100% visualization of the resection margins. Still, recurrences do occur in 2% to 5% of the treated BCCs. It has been suggested that BCC cells in frozen sections stained with hematoxylin and eosin (H&E) may be missed. OBJECTIVE: To determine whether an additional immunohistochemical staining with a cytokeratin marker (MNF 116) indicates BCC cells in sections in which the H&E-stained frozen sections were negative. METHODS: The Mohs procedure was performed under standard conditions in which H&E-stained slides were judged by the Mohs surgeon and the pathologist. After the H&E slides where judged negative, an extra slide was stained using immunohistochemistry and a monoclonal antibody against cytokeratin (MNF 116). RESULTS: A total of 143 complete slides were stained and judged by two Mohs surgeons and a pathologist. One of the 143 slides stained with MNF 116 showed positive staining where the H&E slides were negative, which is 0.7% of the slides. However, this single slide represents a failure of nearly 2% of the treated patients. CONCLUSION: Frozen sections stained with H&E in MMS offer enough security in detecting BCC cells during surgery; however, adjuvant cytokeratin staining can be useful in very selected cases of aggressive growing BCC.

Adult↗
PubMed2003

Inflammation and restenosis: implications for therapy.

Restenosis is the process of luminal narrowing in an atherosclerotic artery after an intra-arterial intervention such as balloon angioplasty and stenting. It is believed that this process is mainly characterized by migration and proliferation of smooth muscle cells and extracellular matrix accumulation. However, there is now increasing evidence for a role of inflammation in the development of restenosis. The underlying molecular mechanisms of restenosis are, in fact, most probably regulated by inflammatory mediators, such as cytokines. Understanding the molecular mechanisms in restenosis is crucial for the development of a suitable therapy for this disease. Recently, the use of immunosuppressives in drug-eluting stents has provided very promising results in the treatment of restenosis. In this review, we will describe the molecular mechanisms involved in restenosis with a focus on the role of inflammation and the use of immunosuppressive therapy.

Coronary Restenosis↗