PubMed Health⌕ Search

Biomedical subjects

Marek W Radomski

Publications and source records attributed to Marek W Radomski.

At least 19 recordsLinked to original sources
PubMed2006

Selectins--potential pharmacological targets?

Recent advances in our (patho)physiological understanding have underpinned the frequent involvement of the protein family of selectins in the progression of serious illnesses, including cancer and cancer metastasis, and immunological diseases, such as asthma, allergy and autoimmune reactions. Moreover, selectins seem to have a role in post-ischemic damage and during transplant failures (e.g. in graft-versus-host disease). Although the interplay between selectins and their counter-receptors and ligands is not always primarily involved in the development of these pathological conditions, selectins have been investigated as potential therapeutic targets for therapeutic intervention. This review focuses on the latest trends and developments in anti-selectin antibodies, anti-selectin receptor antibodies, recombinant selectin counter-receptors, low molecular weight selectin antagonists (glycomimetics), induction of selectin tolerance and selectin-targeted imaging agents.

Animals↗
PubMed2006

Role of matrix metalloproteinases in intestinal inflammation.

Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several structural cells. The balance between MMPs and TIMPs is essential for many physiological processes in the gut. However, imbalance between MMPs and TIMPs plays an important role in the pathophysiology of diverse intestinal inflammatory conditions. We reviewed the role of the MMP/TIMP system in the pathogenesis of intestinal inflammatory diseases and pharmacologic perspectives for the use of compounds that restore the MMP/TIMP balance.

Animals↗
PubMed2006

Protein kinase C delta mediates platelet-induced breast cancer cell invasion.

Platelets play an important role in carcinogenesis, but the underlying molecular mechanisms remain poorly understood. To investigate the effects of platelets on in vitro invasion of MCF7 human breast cancer cells, human MCF7 cells were used to study their interactions with platelets using aggregometry and cell invasion chambers. Zymography and quantitative polymerase chain reaction (PCR) were used to study matrix metalloproteinases (MMPs), whereas Western blot was used to study protein kinase C (PKC) delta in MCF7 cells. We observed that platelets promoted invasion of MCF7 cells (3-fold increase, p<0.05, n=3) and that this process correlated with a dramatic increase in MMP-9 (8 fold-increase, p<0.001, n=3), which is known to facilitate cancer cell invasion. Because both platelets and MCF7 cells have been shown to release MMP-9, we investigated the cellular source that accounted for this increase. The time course and the use of specific protein synthesis inhibitors demonstrated that most of the increase in MMP-9 levels derived from de novo synthesis of this protease by cancer cells. Furthermore, platelets activated PKCdelta in MCF7 cells after 1 h of incubation (18.45+/-4.75% increase, p<0.05, n=4-7), which, in turn, led to an up-regulation of MMP-9 mRNA (from 60+/-20 to 1040+/-100 pg, p<0.001, n=3) and protein levels (18-fold increase, p<0.001, n=3), with the subsequent cell invasion-promoting effects. PKCdelta plays a crucial role in transducing the invasion-promoting effects of platelets in breast cancer cells, and the specific inhibition of PKCdelta may be a strategy to decrease platelet-mediated cancer cell invasion.

Blood Platelets↗
PubMed2006

Matrix metalloproteinase-9 modulates intestinal injury in rats with transmural colitis.

Proteolysis and degradation of extracellular matrix by metalloproteinases (MMPs) may contribute to intestinal injury in inflammatory bowel disease. In the present study, we investigated the pathogenic role of gelatinases (MMP-9 and MMP-2) on transmural colonic injury in a rat model of chronic colitis, which was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). The activity and expression of MMP-2 and MMP-9 were measured in colonic tissue and peripheral neutrophils by fluorescence, zymography, Western blot, or immunohistochemistry at different time-points. Furthermore, myeloperoxidase content in colonic homogenates was analyzed to evaluate inflammation. Finally, morphological changes were assessed following early or delayed administration of CGS-27023-A, a synthetic inhibitor of MMPs. We found that the induction of colitis led to a significant up-regulation in tissue gelatinase concentration, whereas no changes in collagenase activity were observed. In addition, up-regulation of pro-MMP-9, but not of pro-MMP-2, was found on Days 7 and 10 following the induction of colitis. Furthermore, transmural MMP-9 was detected by immunofluorescent staining in the inflamed tissue. Consistent with tissue samples, neutrophils from colitic rats showed a significantly increased activity of pro-MMP-9. Finally, early but not delayed treatment with CGS-27023-A attenuated colonic mucosal injury in rats with TNBS-induced colitis. In conclusion, up-regulation of MMP-9 in peripheral and colonic neutrophils modulates transmural colonic injury in rats with TNBS-induced colitis.

Animals↗
PubMed2006

Platelet aggregation-induced by caco-2 cells: regulation by matrix metalloproteinase-2 and adenosine diphosphate.

Formation of tumor cell-platelet aggregates facilitates hematogenous metastases. However, molecular mechanisms implicated in tumor cell-induced platelet aggregation (TCIPA) in colon cancer are unclear. To investigate mechanisms of TCIPA induced by colon adenocarcinoma cells in vitro, human Caco-2 cells were used to study their interactions with platelets using aggregometry, zymography, phase-contrast microscopy, and flow cytometry. Caco-2-induced platelet aggregation in a concentration-dependent manner. This aggregation resulted in the release of matrix metalloproteinase (MMP)-2, as measured by zymography. In addition, flow cytometry showed a significant up-regulation of activated GpIIb/IIIa, total GpIIb/IIIa, GpIb, and P-selectin receptors on platelets. Inhibition of MMP-2 by phenantroline and degradation of ADP by APT102, respectively, resulted in inhibition of TCIPA. Furthermore, both phenantroline and APT102 significantly down-regulated the surface abundance of platelet receptors. Caco-2 cells aggregate platelets, at least in part, via releasing MMP-2 and ADP. Modulation of MMP-2 and ADP actions could have therapeutic value in colonic cancer.

Adenosine Diphosphate↗
PubMed2006

Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients.

Although major depression (MD) and cardiovascular disease (CVD) have been conclusively linked in the literature, the mechanism associating MD and CVD is yet undetermined. The purpose of this paper is to further investigate a potential mechanism involving nitric oxide (NO) and to examine the effect of the selective serotonin reuptake inhibitor paroxetine on NO production by both platelets and the endothelium. In total, 17 subjects with MD and 12 healthy controls (HCs) with no known history of cardiovascular illness completed the study. Paroxetine was administered to both the MD patients and HCs over an 8-week period, and then medication was discontinued. Blood samples were taken at various times throughout paroxetine treatment and after discontinuation. Plasma NO metabolite (NOx) levels were measured by a chemiluminescence method. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of L-[14C]arginine to L-[(14)C]citrulline. Data were analyzed using t-tests and a linear mixed effects model. Baseline levels of both plasma NOx and platelet NOS activity were significantly lower in subjects with MD compared to HCs. Throughout paroxetine treatment, plasma NOx levels increased in both HCs and MD patients. However, platelet eNOS activity decreased in HCs, while no statistically significant change was evidenced in MD patients. These data suggest that, in MD patients, decreased peripheral production of NO, a potential contributor to increased cardiovascular risk, is modified by administration of the antidepressant paroxetine.

Adult↗
PubMed2006

Increased alveolar and plasma gelatinases activity during postpump syndrome: Inhibition by inhaled nitric oxide.

Postpump syndrome is associated with systemic inflammation. Matrix metalloproteinases (MMP)-2 and -9 contribute to proinflammatory and platelet-activator reactions. Nitric oxide (NO) is involved in the regulation of MMPs. The objectives of our study were to investigate the intensity of inflammation induced by 3 different surgical procedures, the effects of inflammation on the activity of MMPs, and the regulation of inflammation by inhaled NO (20 ppm). Inhaled NO was initiated immediately after tracheal intubation and maintained for the total duration of the experiments. Thirty pigs were equally randomized into 6 groups [sham; sham + NO; cardiopulmonary bypass; bypass + NO; bypass + lipopolysaccharide (1 microg/kg for 50 min); bypass + lipopolysaccharide + NO] and animals were subjected to anesthesia and mechanical ventilation up to 24 h. The levels of MMP-2 and MMP-9 in plasma and bronchoalveolar lavage were measured using zymography. Bypass resulted in a time-dependent rise in MMP activity, an effect potentiated by lipopolysaccharide. Inhaled NO attenuated the effects of bypass + lipopolysaccharide. These results confirm that MMP-2 and MMP-9 are associated with the inflammatory process causing the postpump syndrome. Preemptive and continuous administration of inhaled NO helps to prevent increased MMP-2 and MMP-9 activity.

Animals↗
PubMed2006

Platelet dysfunction in asphyxiated newborn piglets resuscitated with 21% and 100% oxygen.

Hemostatic disturbances are common in asphyxiated newborns after resuscitation. We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or 100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia was induced with an inspired oxygen concentration of 10-15% for 2 h. Piglets were then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21% oxygen. Platelet counts and collagen (2, 5, and 10 microg/mL)-stimulated whole blood aggregation were studied before hypoxia and at 4 h of post-hypoxia/reoxygenation. Platelet function was studied using transmission electron microscopy and by measuring plasma thromboxane B2 (TxB2) and matrix metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated without hypoxia/reoxygenation. The hypoxemic (PaO2 33 mm Hg) piglets developed hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet aggregation ex vivo was impaired as evidenced by a rightward-downward shifting of the concentration-response curves. Electron microscopy showed features of platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased. Resuscitation with 100% but not 21% oxygen increased plasma TxB2 levels. Platelet counts decreased after hypoxia/reoxygenation but were not different between groups during the experiment. Resuscitation of hypoxic newborn piglets caused platelet activation with significant deterioration of platelet aggregation ex vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate the activation of prostaglandin-thromboxane mechanistic pathway.

Animals↗
PubMed2005

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study.

BACKGROUND: Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. METHODS: Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. RESULTS: Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. CONCLUSIONS: Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.

Aged↗
PubMed2005

Nanoparticle-induced platelet aggregation and vascular thrombosis.

Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

Animals↗
PubMed2004

Platelet-leukocyte aggregation induced by PAR agonists: regulation by nitric oxide and matrix metalloproteinases.

Platelet-leukocyte aggregation (PLA) links haemostasis to inflammation. The role of nitric oxide (NO) and matrix metalloproteinases (MMP-1, -2, -3, -9) in PLA regulation was studied. Homologous human platelet-leukocyte suspensions were stimulated with thrombin (0.1-3 nM) and other proteinase activated receptor-activating peptides (PAR-AP), including PAR1AP (0.5-10 microM), PAR4AP (10-70 microM), and thrombin receptor-activating peptide (1-35 microM). PLA was studied using light aggregometry with simultaneous measurement of oxygen-derived free radicals, dual colour flow cytometry, and phase-contrast microscopy. The release of NO was measured using a porphyrinic nanosensor, while MMPs were investigated by Western blot, substrate degradation assays, immunofluorescence microscopy, and flow cytometry. The levels of P-selectin and microparticles (MP) in PLA were measured by flow cytometry. PLA was also characterized using pharmacological agents: S-nitroso-glutathione (GSNO, 0.01-10 microM), 1H-Oxadiazole quinoxalin-1-one (ODQ, 1 microM), N(G)-L-nitro-L-arginine methyl ester (L-NAME, 100 microM) and compounds that modulate the actions of MMPs such as phenanthroline (100 microM), monoclonal anti-MMP antibodies, and purified MMPs. PAR agonists concentration-dependently induced PLA, an effect associated with the release of microparticles (MP) and the translocation of P-selectin to the platelet surface. NO and radicals were also released during PLA. Inhibition of NO bioactivity by the concomitant release of free radicals or by the treatment with L-NAME or ODQ stimulated PLA, while pharmacological administration of GSNO decreased PLA. PAR agonist-induced PLA resulted in the liberation of MMP-1, -2, -3, and -9. During PLA, MMPs were present on the cell surface, as shown by flow cytometry and immunofluorescence. PLA led to the activation of latent MMPs to active MMPs, as shown by Western blot and substrate degradation assays. Inhibition of MMPs actions by phenanthroline and by the antibodies attenuated PLA. In contrast, purified active, but not latent, MMPs amplified thrombin-induced PLA. It is concluded that NO and MMP-1, -2, -3, and -9 play an important role in regulation of PAR agonist-induced PLA.

Blotting, Western↗
PubMed2004

Platelet--cancer interactions: mechanisms and pharmacology of tumour cell-induced platelet aggregation.

During haematogenous metastasis, cancer cells migrate to the vasculature and interact with platelets resulting in tumour cell-induced platelet aggregation (TCIPA). We review: 1. The biological and clinical significance of TCIPA; 2. Molecular mechanisms involved in platelet aggregation by cancer cells; 3. Strategies for pharmacological regulation of these interactions. We conclude that pharmacological regulation of platelet-cancer cell interactions may reduce the impact of TCIPA on cancer biology.

Animals↗
PubMed2004

Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder.

BACKGROUND: Major depression (MD) has been associated with increased cardiovascular mortality in patients with coronary heart disease (CHD) and has been described as an independent risk factor for the development of CHD in healthy subjects; however, the mechanism of the association between MD and CHD remains to be determined. Nitric oxide (NO) plays a major role in cardiovascular regulation, and decreased NO production has been associated with several cardiovascular risk factors. We hypothesized that in patients with MD, NO production by both platelets and the endothelium would be reduced when compared with healthy control subjects (HCs). METHODS: Blood samples were obtained from 15 subjects with MD and 16 HCs with no known history of cardiovascular illness. Plasma NO metabolite (NOx) levels were analyzed by chemiluminescence. Platelet endothelial NO synthase (eNOS) activity was examined through the conversion of l-[(14)C]arginine to l-[(14)C]citrulline. RESULTS: The levels of both plasma NOx and platelet eNOS activity were significantly lower in subjects with MD compared with HCs. CONCLUSIONS: These data suggest that decreased NO production by the vascular wall and platelets might contribute to the increased CHD risk observed in patients with MD.

Adolescent↗
PubMed2003

Membrane type-1 matrix metalloproteinase stimulates tumour cell-induced platelet aggregation: role of receptor glycoproteins.

1. Matrix metalloproteinase-2 (MMP-2) plays a role in agonist- and tumour cell-induced platelet aggregation (TCIPA). 2. MMP-2 is synthesized as a proenzyme and is activated at the cell surface by membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14). 3. The significance of tumour cell-associated MT1-MMP for TCIPA was investigated using human breast carcinoma MCF7 cells stably coexpressing the integrin alphavbeta3 with MT1-MMP, cells expressing alphavbeta3 alone and mock-transfected cells. 4. Western blot and zymography confirmed that alphavbeta3/MT1-MMP cells expressed MT1-MMP and efficiently processed proMMP-2 to MMP-2. 5. Aggregometry, phase-contrast and transmission electron microscopy and flow cytometry were used to characterize TCIPA induced by MCF7 cell lines. 6. The aggregating potency of cells was: alphavbeta3/MT1-MMP >alphavbeta3=mock cells, as shown by aggregometry and phase-contrast microscopy. 7. Electron microscopy revealed close, membrane-membrane interactions between activated platelets and alphavbeta3/MT1-MMP cells during TCIPA. 8. Inhibition of MMP-2 with the neutralizing anti-MMP-2 antibody (5 microg ml(-1)) and o-phenanthroline (100 microm) reduced aggregation induced by alphavbeta3/MT1-MMP cells. 9. TCIPA induced by alphavbeta3/MT1-MMP cells was also reduced by inhibiting the generation and actions of ADP with apyrase (250 microg ml(-1)) and 2-methylthio-AMP (2-MeSAMP) (30 microm), but not N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) (30 microm). 10. Flow cytometry demonstrated that TCIPA enhanced expression of glycoprotein (GP) Ib and IIb/IIIa receptors not only on platelets but also on breast cancer cells. 11. Thus, (a) human breast carcinoma cell surface-associated MT1-MMP, via activating proMMP-2, stimulates TCIPA; (b) ADP amplifies the effects of MMPs via stimulation of P2Y(12) receptors and (c) both tumour- and platelet-derived GPIb and GPIIb/IIIa are involved in the aggregatory effects of MT1-MMP.

Breast Neoplasms↗
PubMed2003

Nitric oxide and cyclic GMP increase the expression of matrix metalloproteinase-9 in vascular smooth muscle.

Interactions and possible cross talk between inducible nitricoxide synthase (iNOS), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), were studied in rat aortic vascular smooth muscle cells stimulated with bacterial lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and phorbol 12-myristate13-acetate (PMA). The expression and activity of iNOS, COX-2, and MMP-9 were characterized at the transcriptional, protein, and enzyme activity levels. The NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) was used to investigate the effects of NO on COX-2 and MMP-9 at the transcriptional level. The measurements of mRNAs for these enzymes using real-time polymerase chain reaction (PCR) showed that COX-2 mRNA was up-regulated 2.3-fold, whereas MMP-9 mRNA up-regulation was 11.7-fold in the presence of LPS, IFN-gamma, and PMA. Real-time PCR results indicated that L-NAME exerted an inhibitory effect on COX-2 and MMP-9 mRNA synthesis. Both superoxide dismutase (SOD) and the SOD mimetic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP) did not modify significantly the up-regulation of these enzymes, indicating that neither superoxide nor peroxynitrite are involved in this mechanism. Furthermore, NO-mediated up-regulation of MMP-9 was cGMP-dependent since 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase, blocked, in a concentration-dependent manner, the increased expression of MMP-9, an effect reversed by 8-bromo-cGMP, a soluble analog of cGMP. Our findings suggest that NO and cGMP are necessary to up-regulate the expression of MMP-9.

Animals↗
PubMed2003

Generation and role of angiostatin in human platelets.

Platelets regulate new blood vessel growth, because they contain a number of angiogenesis promoters and inhibitors. Additionally, platelets contain matrix metalloproteinases (MMPs), which when released mediate platelet adhesion and aggregation, and plasminogen, a fibrinolytic system enzyme that serves to limit blood clot formation. Enzymatic cleavage of plasminogen by MMPs generates angiostatin, an angiogenesis inhibitor. Therefore, we examined whether platelets generate angiostatin during aggregation in vitro. Platelets were isolated from healthy human donors and then aggregated with collagen, thrombin, or HT-1080 fibrosarcoma cells. Angiostatin was detected by Western blot analysis in the platelet releasates of all blood donors irrespective of the aggregating agent used. Platelet pellet homogenates showed the presence of angiostatin in all donors, which was released upon aggregation. Furthermore, platelet-derived angiostatin was isolated and purified by lysine-Sepharose affinity chromatography from collagen-aggregated platelet releasates. Bioassay of platelet-derived angiostatin showed that it inhibited the formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in an in vitro angiogenesis model. Inhibition of angiostatin in platelet releasates promoted the formation of capillary structures by HUV-EC-Cs. We conclude that healthy human platelets contain angiostatin, which is released in active form during platelet aggregation, and platelet-derived angiostatin has the capacity to inhibit angiogenesis.

Angiogenesis Inhibitors↗
PubMed2003

Release of matrix metalloproteinase-9 during balloon angioplasty in patients with stable angina. A preliminary study.

BACKGROUND: Vascular wall remodeling is a major factor contributing to restenosis after angioplasty that involves migration and proliferation of vascular smooth muscle cells. The release of matrix-degrading metalloproteinases, including metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental data suggest that nitric oxide (NO) decreases the activity of metalloproteinases and this may attenuate arterial remodeling after balloon injury. We investigated whether metalloproteinase-2, metalloproteinase-9 and NO are released into the coronary sinus blood during angioplasty in coronary patients. METHODS: In 10 patients with stable angina undergoing elective percutaneous transluminal coronary angioplasty of an isolated stenosis of the proximal left anterior descending coronary artery, blood was sampled from the coronary sinus at baseline, immediately and 1 min after each balloon deflation. Plasma release of metalloproteinase-2 and metalloproteinase-9 was assayed by their gelatinolytic activity using zymography, while the liberation of NO metabolites was measured by high-performance liquid chromatography. RESULTS: Two consecutive balloon inflations each of 60 s duration, resulted in an immediate increase (P<0.05) of metalloproteinase-9, but not metalloproteinase-2 activity, followed by normalization of metalloproteinase-9 levels to the baseline within 1 min. Plasma levels of NO metabolites remained unchanged. CONCLUSIONS: Rapid release of metalloproteinase-9 after balloon inflation may both contribute to remodeling and protect the vascular wall from post-angioplasty thrombosis.

Angina Pectoris↗