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Common pathways of hypercholesterolemia and hypertension leading to atherothrombosis: the need for a global approach in the management of cardiovascular risk factors

By José Tuñón, José Luis Martín-Ventura, Luis Miguel Blanco-Colio, Nieves Tarín and Jesús Egido


In the last years there has been increasing evidence suggesting that the treatment of cardiovascular risk factors must be done on a global rather than on a separate approach, because they have additive effects and share common pathways leading to atherothrombosis. Of special interest is the relationship between hypertension and dyslipidemia. An excessive activity of the renin-angiotensin system (RAS), that plays an important role in hypertension, contributes to endothelial dysfunction, vascular inflammation and thrombosis. Dyslipidemia induces the same effects through similar mechanisms. In fact, combined therapy with statins and RAS modulators shows synergic beneficial effects in the treatment of atherosclerosis. Then, in the future, the traditional hypertension and dyslipidemia units should probably evolve into global cardiovascular risk management Units. Also, polypills combining antihypertensive and lipid-lowering drugs will make easier the treatment of these conditions. These changes would provide us the necessary tools to treat our patients in accordance with the current strategies of cardiovascular therapy and prevention

Topics: Review
Publisher: Dove Medical Press
OAI identifier: oai:pubmedcentral.nih.gov:2291342
Provided by: PubMed Central
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    1. (1998). 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fi brinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho proteins. Circ Res,
    2. (1997). Angiotensin Converting enzyme inhibition prevents arterial NF-kB activation, MCP-1 expression and macrophage infi ltration in a rabbit model of early accelerated atherosclerosis.
    3. (1999). Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein.
    4. (2006). Angiotensin II induces the expression of tissue factor and its mechanism in human monocytes. Thromb Res,
    5. (1997). Angiotensin II injection into mice increases the uptake of oxidized LDL by their macrophages via a proteoglycanmediated pathway.
    6. (2003). Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinfl ammatory action.
    7. (1996). Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations to vasomotor tone.
    8. (1997). Angiotensin-converting enzyme inhibition abolishes medial smooth muscle PDGF-AB biosynthesis and attenuates cell proliferation in injured carotid arteries: relationships to neointima formation.
    9. (1996). Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease.
    10. (2003). Antiinfl ammatory and immunomodulatory effects of statins.
    11. (2004). Antiinfl ammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinfl ammation.
    12. (2007). Atorvastatin modifies the protein profile of circulating human monocytes after an acute coronary syndrome.
    13. (1999). Atorvastatin reduces NF-κB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells.
    14. (2002). Atorvastatin reduces the expression of cyclooxygenase-2 in a rabbit model of atherosclerosis and in cultured vascular smooth muscle cells.
    15. (2004). Blockade of the angiotensin II type 1 receptor stabilizes atherosclerotic plaques in humans by inhibiting prostaglandin E2-dependent matrix metalloproteinase activity.
    16. (2004). Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of infl ammation and platelet aggregation in patients with coronary artery disease.
    17. (2003). Connective tissue growth factor is a mediator of angiotensin II-induced fi brosis.
    18. (2006). Cross-talk between dyslipidemia and renin-angiotensin system and the role of
    19. (2002). Effect of angiotensin II on microvascular permeability.
    20. (2005). Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and infl ammation in type 2 diabetic patients.
    21. (1999). Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia.
    22. (2000). Effects of an angiotensin-convertingenzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.
    23. (1994). Effects of captopril therapy on endogenous fi brinolysis in men with recent, uncomplicated myocardial infarction.
    24. (1995). Effects of losartan on contractile responses of conductance and resistance arteries from rats.
    25. (2004). Endothelial dysfunction, infl ammation and statins: new evidences. Rev Esp Cardiol,
    26. (1996). Erratum in: Circulation,
    27. (2000). Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for infl ammation and plaque instability.
    28. (1961). Factors of risk in the development of coronary heart disease—six year follow-up experience. The Framingham Study. Ann Intern Med,
    29. (2003). HDL counterbalance the proinfl ammatory effect of oxidized LDL by inhibiting intracellular reactive oxygen species rise, proteasome activation, and subsequent NF-kappaB activation in smooth muscle cells.
    30. (2000). HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol,
    31. (1998). HMG-CoA reductase inhibition by atorvastatin reduces neointimal infl ammation in a rabbit model of atherosclerosis.
    32. (2005). HMG-CoA reductase inhibitors reduce I kappa B kinase activity induced by oxidative stress in monocytes and vascular smooth muscle cells.
    33. (1993). Identifi cation of AT1 receptors on human platelets and decreased angiotensin II binding in hypertension. J Hypertens Suppl,
    34. (1996). Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease.
    35. (1999). Increased NADHoxidase-mediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system.
    36. (1992). Increased thromboxane biosynthesis in type IIa hypercholesterolemia.
    37. (2003). Induction of connective tissue growth factor by angiotensin II: integration of signaling pathways.
    38. (1995). Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol,
    39. (2005). Intensive treatment with atorvastatin reduces infl ammation in mononuclear cells and human atherosclerotic lesions in one month.
    40. (2000). Lovastatin inhibits transforming growth factor-beta1 expression in diabetic rat glomeruli and cultured rat mesangial cells. J Am Soc Nephrol,
    41. (1996). Major risk factors and primary prevention: Overview. In: Fuster V, Ross R, Topol E (eds). Atherosclerosis and coronary artery disease. Philadelphia: Lippincott-Raven,
    42. (2002). MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
    43. (1999). Novel mechanism for endothelial dysfunction. Dysregulation of dimethylarginine dimethylaminohydrolase.
    44. (1997). Nuclear factor-κB. A pivotal transcription factor in chronic infl ammatory diseases.
    45. (1999). Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages.
    46. (1998). p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy.
    47. (1995). Peroxynitrite-mediated oxidative protein modifi cations.
    48. (2002). Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human vascular smooth muscle cells.
    49. (2004). Role of angiotensin II in ischemia/reperfusion-induced leukocyte-endothelium interactions in the colon.
    50. (2005). Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).
    51. (1995). Role of the fi brinolytic system in preventing myocardial infarction. Eur Heart J, 16(Suppl K):31–6.
    52. (1993). Simvastatin inhibits PDGF-induced DNA synthesis in human glomerular mesangial cells. Kidney Int,
    53. (2002). Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.
    54. (1997). Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.
    55. (2002). Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways.
    56. (1999). Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men.
    57. (2003). Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol,
    58. (1998). The ACE inhibitor quinapril reduces the arterial expression of NF-κB dependent proinfl ammatory factors but not of collagen in a rabbit model of atherosclerosis.
    59. (1995). The endothelial cell nitric oxide synthase: is it really constitutively expressed? Agents Actions Suppl,
    60. (2005). The potential relevance of the multiple lipidindependent (pleiotropic) effects of statins in the management of acute coronary syndromes.
    61. (1997). Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.
    62. (1988). Treatment of hypertension with captopril: preservation of regional blood fl ow and reduced platelet aggregation.
    63. (1998). Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors.
    64. (1997). Upregulation of vascular angiotensin II receptor gene expression by low-density lipoprotein in vascular smooth muscle cells.

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