Cardiovascular disease is the leading cause of death through – out the world 1 WHO.Cardiovascular diseases (CVDs) Fact sheet N┬░317; September 2012. . The main condition underlying cardiovascular events is atherosclerosis. The ‘modifiable risk factors’, i.e. hyperten- sion, hyperlipidaemia, diabetes mellitus, obesity and smoking, play a crucial role in the genesis of this condition, in addition to genetic background. Before final cardiovascular events (heart attack and stroke) which are nothing more than the end results of atherosclerosis, become clinically apparent, the arterial wall undergoes a malfunction as a result of the continuous harmful action exerted by various risk factors, which primarily affect the endothelium and is therefore known as ÔÇ£endothelial dysfunctionÔÇØ. The endothelium regulates vascular tone in response to physical and chemical stimuli by releasing vasodilating substances such as nitric oxide (NO), prostacyclin and bradykinin as well as vasoconstrictor molecules such as endothelin and angiotensin II. In this context, NO is the main mediator of all the vasoprotective effects because it is not only a potent vasodilator but also possesses anti-inflammatory, antiproliferative and antithrombotic properties 2 Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004; 109 (23 Suppl 1):III27-32. . Continuous oxidative stress induced by cardiovascular risk factors gives rise to a reduced bioavailability of NO due to decreased production and/or increased deactivation by free radicals, which is responsible for the onset of the endothelial dysfunction that precedes and promotes the development of atherosclerosis 3 Lubos E, Handy DE, Loscalzo J. Role of oxidative stress and nitric oxide in atherothrombo- sis. Front Biosci. 2008; 13:5323-44. 4 Leopold JA, Loscalzo J. Oxidative risk for atherothrombotic cardiovascular disease. Free Radic Biol Med. 2009; 47:1673-706. 5 Victor VM, Rocha M, Sol├í E, et al. Oxidative stress, endothelial dysfunction and atheroscle- rosis. Curr Pharm Des. 2009; 15:2988-3002. . Oxidative stress also induces the expression of pro-inflammatory mediators that contribute actively to the initial stages of atherogenesis 6 Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evi- dence (risk factors through stable coronary artery disease). Circulation. 2006; 114:2850-70. 7 Koenen RR, Weber C. Manipulating the chemokine system: therapeutic perspectives for ath- erosclerosis. Curr Opin Investig Drugs. 2010; 11:265-72. .

It has long been that the inhabitants of the Mediterranean area have a lower incidence of cardiovascular events than Nordic peoples and this has been attributed mainly to diet and, in particular, the consump tion of tomatoes, of which lycopene is the main constituent 8 Rogers L. CardioPulse: Lycopene: the path to a healthier heart? Eur Heart J. 2010; 31:512-4. . Buijsse B, et al. found that elderly men in Crete had lower blood levels of oxidative stress markers at the same time as lycopene levels that were four times higher than their contemporaries in a Dutch village 9 Buijsse B, Feskens EJ, Moschandreas J, et al. Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil. 2007; 14:495-500. (Figure 4). Some epidemiological studies suggested that the intake of foods containing lycopene and blood levels of this substance are inversely related to the incidence of cardiovascular disease 10
Petr L, Erdman JW. Lycopene and risk of cardiovascular disease. In: Packer L, Obermuller- Jevic U, Kraemer K, Sies H, editors. Carotenoids and retinoids: molecular aspects and health is- sues. Champaign: AOCS Press; 2005. pp. 204-217.
11 Voutilainen S, Nurmi T, Mursu J, Rissanen TH. Carotenoids and cardiovascular health. Am J Clin Nutr. 2006; 83:1265-71. . This trend was also confirmed for ischaemic stroke by data emerging from a study conducted in Finland 12 Karppi J, Laukkanen JA, Sivenius J, et al. Serum lycopene decreases the risk of stroke in men: A population-based follow-up study. Neurology. 2012; 79:1540-7. . Two recent reviews 13 Mordente A, Guantario B, Meucci E, et al. Lycopene and cardiovascular diseases: an up- date. Curr Med Chem. 2011; 18:1146-63. 14 B├Âhm V. Lycopene and heart health. Mol Nutr Food Res. 2012; 56:296-303. nevertheless pointed out that the data in the literature are not unequivocal. It should be emphasised, however, that the majority of studies nevertheless suggest a significant inverse association between plasma or tissue levels of lycopene and the incidence of cardiovascular disease or of its risk factors 15Mordente A, Guantario B, Meucci E, et al. Lycopene and cardiovascular diseases: an up- date. Curr Med Chem. 2011; 18:1146-63. .

Some studies indicate that lycopene may have a favourable effect on several of these risk factors. In human macrophages lycopene reduces total intracellular choles – terol in a dose-dependent manner in vitro: this effect is associated with inhibition of HMG-CoA reductase, modulation of the LDL receptor and activity of the enzyme acyl-coenzyme A:cholesterol acyltransferase 16 Palozza P, Catalano A, Simone RE, et al. Effect of lycopene and tomato products on choles- terol metabolism. Ann Nutr Metab. 2012; 61:126-134. (Figure 5). A meta-analysis of intervention studies in humans between 1995 and 2010 to assess the effect of lycopene on plasma lipids and blood pressure revealed that this carotenoid, when taken at a daily dose of > 25 mg, is effective in reducing both total cholesterol and LDL cholesterol 17 Palozza P, Catalano A, Simone RE, et al. Effect of lycopene and tomato products on cholesterol metabolism. Ann Nutr Metab. 2012; 61:126-134. . Although the number of clinical studies on blood pressure is still low (n = 4), the meta-analysis showed a significant reduction in systolic values, particularly in hypertensive patients 18 Ried K, Fakler P. Protective effect of lycopene on serum cholesterol and blood pressure: Meta-analyses of intervention trials. Maturitas. 2011; 68:299-310. . Studies carried out on platelet function showed that lycopene exerts an antithrombotic effect by reducing the activation and clumping of these blood factors in vitro and in vivo in humans 19 O’Kennedy N, Crosbie L, van Lieshout M, et al. Effects of antiplatelet components of toma- to extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans. Am J Clin Nutr. 2006; 84:570-9. 20 O’Kennedy N, Crosbie L, Whelan S, et al. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am J Clin Nutr. 2006; 84:561-9. . The action exercised by lycopene on cardiovascular risk factors may explain the improvement that it brings about in vivo on endothelial function 21 B├Âhm V. Lycopene and heart health. Mol Nutr Food Res. 2012; 56:296-303. 22 Palozza P, Catalano A, Simone RE, et al. Effect of lycopene and tomato products on choles- terol metabolism. Ann Nutr Metab. 2012; 61:126-134. and on the early development of atherosclerosis 23 Gianetti J, Pedrinelli R, Petrucci R, et al. Inverse association between carotid intima-me- dia thickness and the antioxidant lycopene in atherosclerosis. Am Heart J. 2002; 143:467-74 24
Riccioni G, D’Orazio N, Speranza L, et al.Carotenoids and asymptomatic carotid atheroscle- rosis. J Biol Regul Homeost Agents. 2010; 24:447-52.
(Figure 6).

References   [ + ]

1. WHO.Cardiovascular diseases (CVDs) Fact sheet N┬░317; September 2012.
2. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004; 109 (23 Suppl 1):III27-32.
3. Lubos E, Handy DE, Loscalzo J. Role of oxidative stress and nitric oxide in atherothrombo- sis. Front Biosci. 2008; 13:5323-44.
4. Leopold JA, Loscalzo J. Oxidative risk for atherothrombotic cardiovascular disease. Free Radic Biol Med. 2009; 47:1673-706.
5. Victor VM, Rocha M, Solá E, et al. Oxidative stress, endothelial dysfunction and atheroscle- rosis. Curr Pharm Des. 2009; 15:2988-3002.
6. Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evi- dence (risk factors through stable coronary artery disease). Circulation. 2006; 114:2850-70.
7. Koenen RR, Weber C. Manipulating the chemokine system: therapeutic perspectives for ath- erosclerosis. Curr Opin Investig Drugs. 2010; 11:265-72.
8. Rogers L. CardioPulse: Lycopene: the path to a healthier heart? Eur Heart J. 2010; 31:512-4.
9. Buijsse B, Feskens EJ, Moschandreas J, et al. Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil. 2007; 14:495-500.
10.
Petr L, Erdman JW. Lycopene and risk of cardiovascular disease. In: Packer L, Obermuller- Jevic U, Kraemer K, Sies H, editors. Carotenoids and retinoids: molecular aspects and health is- sues. Champaign: AOCS Press; 2005. pp. 204-217.
11. Voutilainen S, Nurmi T, Mursu J, Rissanen TH. Carotenoids and cardiovascular health. Am J Clin Nutr. 2006; 83:1265-71.
12. Karppi J, Laukkanen JA, Sivenius J, et al. Serum lycopene decreases the risk of stroke in men: A population-based follow-up study. Neurology. 2012; 79:1540-7.
13. Mordente A, Guantario B, Meucci E, et al. Lycopene and cardiovascular diseases: an up- date. Curr Med Chem. 2011; 18:1146-63.
14. B├Âhm V. Lycopene and heart health. Mol Nutr Food Res. 2012; 56:296-303.
15. Mordente A, Guantario B, Meucci E, et al. Lycopene and cardiovascular diseases: an up- date. Curr Med Chem. 2011; 18:1146-63.
16, 22. Palozza P, Catalano A, Simone RE, et al. Effect of lycopene and tomato products on choles- terol metabolism. Ann Nutr Metab. 2012; 61:126-134.
17. Palozza P, Catalano A, Simone RE, et al. Effect of lycopene and tomato products on cholesterol metabolism. Ann Nutr Metab. 2012; 61:126-134.
18. Ried K, Fakler P. Protective effect of lycopene on serum cholesterol and blood pressure: Meta-analyses of intervention trials. Maturitas. 2011; 68:299-310.
19. O’Kennedy N, Crosbie L, van Lieshout M, et al. Effects of antiplatelet components of toma- to extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans. Am J Clin Nutr. 2006; 84:570-9.
20. O’Kennedy N, Crosbie L, Whelan S, et al. Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am J Clin Nutr. 2006; 84:561-9.
21. B├Âhm V. Lycopene and heart health. Mol Nutr Food Res. 2012; 56:296-303.
23. Gianetti J, Pedrinelli R, Petrucci R, et al. Inverse association between carotid intima-me- dia thickness and the antioxidant lycopene in atherosclerosis. Am Heart J. 2002; 143:467-74
24.
Riccioni G, D’Orazio N, Speranza L, et al.Carotenoids and asymptomatic carotid atheroscle- rosis. J Biol Regul Homeost Agents. 2010; 24:447-52.