**3. Atheroprotective strategies**

peroxidase, uncoupled nitric oxide synthase, lipoxygenases and mitochondrial electron transport chain [20,21,22]. Ox-LDL particles exhibit multiple atherogenic properties, which include uptake and accumulation of macrophages, as well as pro-inflammatory, immuno‐ genic, apoptotic and cytotoxic activities, induction of the expression of adhesion molecules on endothelial cells, promotion of monocyte differentiation into macrophages, production

In particular, at endothelial level, ROS regulates numerous signaling pathways including those regulating growth, proliferation, inflammatory responses of endothelial cells, barrier function and vascular remodeling; while at VSMC level, ROS mediates growth, migration, matrix regulation, inflammation and contraction [23,24,25], all are critical factors in the pro‐

A vicious cycle between oxidative stress and oxidative stress-induced atherosclerosis leads

**Figure 3.** Role of ROS and oxidative stress in the atherosclerosis. Modified from [24]. O2: oxygen; O2

hydrogen peroxide; VSMC: vascular smooth muscle cell.


: superoxide; H2O2:

and release of pro-inflammatory cytokines and chemokines from macrophages [14].

gression and complication of atherosclerosis.

4 Current Trends in Atherogenesis

to the development and progression of atherosclerosis.

Recently, various pharmacological therapies have been designed to reduce the development and progression of the atherosclerotic plaque and remarkable therapeutic advances in the treatment of CVDs have been made with insulin sensitizers, statins, inhibitors of the reninangiotensin system and anti-platelet agents [19,26]. However, strictly control of cardiovascu‐ lar risk factors are often difficult to obtain and the progression of atherosclerosis has not been completely prevented with current pharmacological therapeutic options. Moreover, the modern evolution of Western societies seemingly steers populations towards a profound sedentary lifestyle and incorrect diet is becoming difficult to reverse. Understanding of the mechanisms that explain the fatal effects of physical inactivity and incorrect diet, the benefi‐ cial effects of an healthy lifestyle remains largely unexplored [3].

Concerning atherosclerosis prevention by foods, dietary supplements and healthy life style may provide prevention and/or treatment to the onset and development of atherosclerosis. Development of an atheroprotective strategy acting on oxidative stress involved in the pathogenesis of atherosclerosis and with little toxicity or adverse effects may provide an ide‐ al therapeutic treatment for atherosclerosis. Actually, numerous studies have investigated the prevention and treatment of atherosclerosis using naturally-occurring anti-oxidants.

In this review we summarize the many pieces of the puzzle to identified molecular targets for prevention and therapy against atherosclerosis and present that a healthy life style has natural anti-atherogenic activity which has been forgotten by modern societies.

**Figure 4.** Potential atheroprotective role of anti-oxidants in the atherogenic process. Modified from [27]. ox-LDL: oxi‐ dized-low density lipoprotein; ROS: reactive oxygen species.
