Monica Canavesi

University of Milan, Milano, Lombardy, Italy

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Publications (44)153.64 Total impact

  • Atherosclerosis Supplements 06/2010; 11(2):92-92. DOI:10.1016/S1567-5688(10)70423-2 · 2.29 Impact Factor
  • S Bellosta · M Canavesi · A de Francesco · C Anelli · A Corsini
    Atherosclerosis Supplements 06/2009; 10(2). DOI:10.1016/S1567-5688(09)70880-3 · 2.29 Impact Factor
  • Atherosclerosis Supplements 06/2009; 10(2). DOI:10.1016/S1567-5688(09)70883-9 · 2.29 Impact Factor
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    ABSTRACT: Monocytes/macrophages recruited into the arterial wall during atherogenesis are crucial in the initiation and progression of atherosclerosis and play a fundamental role in the destabilization process that is the main causal event of acute coronary syndromes. In the present study, we investigated the effect of the mammalian target of rapamycin inhibitor everolimus on macrophage accumulation within carotid lesions elicited by perivascular collar placement in cholesterol-fed rabbits. Everolimus (1.5 mg/kg given 1 day before collaring followed by 1 mg/kg/day for 14 days, administered by oral gavage) markedly decreased lesion macrophage content as compared with vehicle control (-65%; p < 0.01). This effect was associated with a reduction in intimal thickening and occurred in the absence of changes in plasma cholesterol concentrations. To gain insights on the potential mechanism(s) underlying this effect, we investigated the influence of everolimus on chemoattractant-induced migration of human monocytes in vitro. Pretreatment with therapeutic concentrations of everolimus (10 nM) significantly lowered monocyte chemotaxis in response to various chemotactic factors (i.e., monocyte chemoattractant protein-1/CCL2, fractalkine/CX3CL1, interleukin-8/CXCL8, complement fragment 5a, or N-formyl-Met-Leu-Phe) without inducing monocyte cell death. These results suggest that everolimus may favorably influence the atherosclerotic process by affecting the recruitment of monocytes into early lesions.
    Journal of Pharmacology and Experimental Therapeutics 12/2008; 328(2):419-25. DOI:10.1124/jpet.108.144147 · 3.97 Impact Factor
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    ABSTRACT: Metalloproteinases (MMPs) are zinc-dependent endopeptidases responsible for the hydrolysis of various component of extracellular matrix such as gelatin and collagen. MMPs, namely MMP-2 and MMP-9 correlate with cardiovascular events in patients. We sought to determine whether supplementation with polyphenol-rich Cynara cardunculus (wild artichoke, traditional component of the Mediterranean diet) modulates MMP-9 expression and activity in cell cultures. A fully characterized C. cardunculus extract was able to inhibit, in a dose-dependent manner, the gelatinolytic activity of secreted MMP-9 and both secretion and human MMP-9 promoter-driven transcription. Analysis by HPLC of the Cynara extract identified polyphenols such as luteolin, apigenin, and caffeic acid, among others. However, testing a mix of the individual components suggested that the inhibitory effects of C. cardunculus are due to minor constituent fraction(s) as a whole. In promoting the health benefits of the Mediterranean diet, the role of wild plants as important meal components deserves further reappraisal.
    Molecular Nutrition & Food Research 10/2008; 52(10):1147-52. DOI:10.1002/mnfr.200700502 · 4.60 Impact Factor
  • Atherosclerosis Supplements 05/2008; 9(1):165-166. DOI:10.1016/S1567-5688(08)70666-4 · 2.29 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate both integrity and composition of the extracellular matrix (ECM). Excessive ECM breakdown by MMPs is implicated in many physiological and pathological conditions, such as atherosclerosis. Activated macrophages, especially in the atherosclerotic lesion, are a major source of reactive oxygen species (ROS). Antioxidants protect against ROS-induced MMPs activation and inhibit gelatinolytic activity. We sought to determine whether the antioxidants glutathione (GSH), N-acetylcysteine (NAC), or lipoic acid (LA) affect gelatinase production and secretion. The results show that thiol compounds affect MMPs expression and activity in different ways. MMP-2 activity is directly inhibited by NAC and GSH, while LA is ineffective. On the contrary, MMP-9 expression is inhibited by LA at a pretrascriptional level, and MMP-9 activity is stimulated by GSH through a direct interaction with the gelatinase itself. Although all thiols, these compounds have different properties and different cellular uptakes and metabolic characteristics, and this could explain, at least in part, their differential effects on MMPs.
    Biochemical and Biophysical Research Communications 12/2007; 363(3):651-5. DOI:10.1016/j.bbrc.2007.09.018 · 2.30 Impact Factor
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    ABSTRACT: Secretion of matrix metalloproteinases (MMPs) by macrophages and smooth muscle cells (SMC) may impair atherosclerotic cap integrity leading to atherosclerosis complications. Selective estrogen receptor modulators (SERMs) have favourable impact on plasma lipid levels, but their role in the prevention of atherosclerosis still remains unclear. We investigated the effects of raloxifene, a second generation SERM, on MMP expression and activity in cultured macrophages and SMC, and in rabbit carotid lesions. Human monocyte-derived macrophages were isolated from blood of healthy donors. SMC were isolated from the intima-media layers of collared rabbit carotid arteries. Cells were incubated for 24h with increasing concentrations of raloxifene. Ovariectomized rabbits fed a 1% cholesterol-rich diet were subjected to pericarotid collar placement and treated with or without 10mgkg(-1)d(-1) raloxifene for 2 weeks. In macrophages, raloxifene treatment (0.1-10microM) significantly reduced MMP-9 gelatinolytic potential in a concentration-dependent manner, without affecting MMP-9 activation. This effect was estrogen receptor (ER)-dependent and due to the inhibition of MMP-9 promoter-driven transcription following an interaction with NF-kB pathway. Similarly, in cultured SMC, raloxifene inhibited up to 40% MMP-2 gelatinolytic activity. In vivo, raloxifene decreased the expression of MMP-2, MMP-3, and MMP-9 by intimal cells and the total gelatinolytic activity of collared carotids. These effects were accompanied by reduction of lesion size and inhibition of macrophage accumulation. Overall, results indicate that raloxifene may reduce MMPs expression and activity in macrophages and smooth muscle cells and favourably affect lesion formation.
    Pharmacological Research 09/2007; 56(2):160-7. DOI:10.1016/j.phrs.2007.05.004 · 4.41 Impact Factor
  • Atherosclerosis Supplements 06/2007; 8(1):71-71. DOI:10.1016/S1567-5688(07)71228-X · 2.29 Impact Factor
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    ABSTRACT: Inflammation contributes importantly to all stages of atherosclerosis, including the onset of acute thrombotic complications. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. Moreover, statins have been shown to possess several pleiotropic properties independent of cholesterol lowering in experimental settings. Based on these premises, we investigated the anti-inflammatory and anti-atherothrombotic properties of rosuvastatin in vivo, testing its effect on cholesterol and monocyte accumulation, and on adhesion molecules and tissue factor (TF) expression. ApoE-deficient female mice were fed a cholesterol-rich diet containing rosuvastatin (0, 1, 2 or 10 mg kg(-1)d(-1)) for 12 weeks. Treatment with rosuvastatin did not significantly affect either body weight gain or plasma total cholesterol (C) and triglyceride levels. However, rosuvastatin treatment dose-dependently reduced ICAM-1 expression in the aortic valves (V) (up to 40% inhibition, p<0.05) and in the proximal segment of the ascending aorta (AA) (-50%, p<0.001). Similarly, rosuvastatin inhibited VCAM-1 expression in the V (-40%) and in the AA (-35%, p<0.05). Moreover, there was a reduced accumulation of macrophages in the V in a dose-dependent and statistically significant manner (-45%, p<0.01). These anti-inflammatory effects were reflected in a reduction of cholesterol deposition in the entire aorta, both in the free and in the esterified form. Finally, the expression of tissue factor, the most potent pro-thrombogenic agent, was consistently reduced in AA by rosuvastatin treatment (-71%, p<0.001). Altogether, these data demonstrate that rosuvastatin has anti-inflammatory and anti-atherothrombotic activities in apoE-deficient mice that could translate in a beneficial effect on atherogenesis.
    Pharmacological Research 05/2007; 55(5):441-9. DOI:10.1016/j.phrs.2007.02.001 · 4.41 Impact Factor
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    ABSTRACT: Salt-loaded, spontaneously hypertensive stroke-prone rats show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive stroke-prone rats over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive stroke-prone rats euthanized at different stages of proteinuria showed progressive inflammatory cell infiltration, the accumulation of alpha-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe fibrosis. These were accompanied by an imbalance in the plasminogen/plasmin and metalloprotease systems characterized by the increased renal expression of plasminogen activator inhibitor-1, tissue plasminogen activator, and urokinase plasminogen activator; the net result was an increase in plasmin and matrix metalloproteinase (MMP)-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic rosuvastatin had renoprotective effects in terms of morphology and inflammation and prevented the changes in plasmin, MMP-2, and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma lipid levels. Treatment with the lipophilic simvastatin was not renoprotective. These data suggest that rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by inflammation and fibrosis.
    American Journal Of Pathology 04/2007; 170(4):1165-77. DOI:10.2353/ajpath.2007.060882 · 4.59 Impact Factor
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    ABSTRACT: High density lipoproteins (HDL) protect the heart against ischemia/reperfusion (I/R) injury, and matrix metalloproteinase-2 (MMP-2) directly contributes to cardiac contractile dysfunction after I/R. To investigate the possible involvement of MMP-2 inhibition in HDL-mediated cardioprotection, isolated rat hearts underwent 20 min of low-flow ischemia and 30 min of reperfusion. Plasma-derived and synthetic HDL attenuated the I/R-induced cardiac MMP-2 activation and release in a dose-dependent way. The attenuation of I/R-induced MMP-2 activation by HDL correlated with the reduction of post-ischemic contractile dysfunction and cardiomyocyte necrosis. These results indicate prevention of MMP-2 activation as a novel mechanism for HDL-mediated cardioprotection.
    FEBS Letters 11/2006; 580(25):5974-8. DOI:10.1016/j.febslet.2006.10.006 · 3.17 Impact Factor
  • Atherosclerosis Supplements 06/2006; 7(3):566-566. DOI:10.1016/S1567-5688(06)82290-7 · 2.29 Impact Factor
  • R. Parente · M. Canavesi · N. Ferri · M. Sani · M. Zanda · S. Bellosta
    Atherosclerosis Supplements 06/2006; 7(3):244-244. DOI:10.1016/S1567-5688(06)80974-8 · 2.29 Impact Factor
  • Atherosclerosis Supplements 06/2006; 7(3):463-464. DOI:10.1016/S1567-5688(06)81862-3 · 2.29 Impact Factor
  • 14th Meeting of the International-Society-of-Atherosclerosis; 06/2006
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    ABSTRACT: Catechins are able to modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages. Gallocatechins decrease MMP-9 secretion by lowering MMP-9 promoter activity and mRNA levels. The effect appears to be dependent on some structural and stereochemical requirements. In this study, the relationship between chemical structure and activity was studied by testing the effect of analogues of (+/-)-gallocatechin-3-gallate (+/-)-GCG, selectively deprived of hydroxyl groups, on MMP-9 activity, transcription, and secretion. Our results indicate that (+/-)-GCG and (+/-)-catechin-3-gallate are characterized by a substitution pattern compatible with direct inhibition of MMP-9 activity. Conversely, when transcription was the target, (+/-)-trans-3-flavanol-3-benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter activity and consequently protein secretion, and in inhibiting nuclear-factor-kappaB-driven transcription. Our results suggest that the structural requirements for enzyme inhibition are different from those necessary for targeting gene expression.
    Cellular and Molecular Life Sciences CMLS 06/2006; 62(23):2896-903. DOI:10.1007/s00018-005-5422-7 · 5.81 Impact Factor
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    ABSTRACT: We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.
    FEBS Letters 01/2006; 579(29):6537-42. DOI:10.1016/j.febslet.2005.10.042 · 3.17 Impact Factor
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    ABSTRACT: The interaction of cells with the extracellular matrix (ECM) is critical for the normal development and function of organisms. The matrix metalloproteinases (MMPs) are a family of Zn(++) and Ca(++) dependent endopeptidases, which are key mediators of ECM remodelling. The turnover and remodelling of ECM must be tightly regulated, since uncontrolled proteolysis would contribute to abnormal development and to the generation of many pathological conditions characterized by either excessive degradation, or lack of degradation of ECM components. In particular, the gelatinases (MMP-2 and -9) are abundantly expressed in various malignant tumors, play an active role in angiogenesis, and may also influence the process of atherosclerotic lesion formation. In recent years, much consideration has been given to the role of diet in preventing degenerative diseases, such as cancer and cardiovascular diseases. Polyphenols are abundant components/micronutrients of the human diet that have been shown in vitro to profoundly affect ECM turnover by regulating gelatinases expression and activity, acting at both the pre- and post-transcriptional level. Therefore, they could have a beneficial effect in many pathological conditions implicated in connective tissue destruction and remodelling associated with degenerative diseases.
    Thrombosis and Haemostasis 05/2005; 93(4):751-60. DOI:10.1267/THRO05040751 · 4.98 Impact Factor
  • R Parente · G Candiani · M Canavesi · F Pecker · M Sani · M Zanda · S Bellosta
    6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular; 05/2005

Publication Stats

1k Citations
153.64 Total Impact Points


  • 1997–2009
    • University of Milan
      • Department of Pharmacological Sciences
      Milano, Lombardy, Italy
    • University of California, Berkeley
      • Lawrence Berkeley Laboratory
      Berkeley, California, United States
  • 2005
    • Centro Cardiologico Monzino
      Milano, Lombardy, Italy