**4. Conclusion**

There is sufficient evidence to show that insulin resistance and hyperinsulinism produce significant changes at the vascular level [7, 25, 32, 36, 37]. The proposed mechanisms are (1) the IGF-1 receptor, (2) through the coactivation between IG-1 and AT1R, (3) by activating nuclear transcription factors such as NF-KB or AP-1, (4) by dimerization of IL-6R, and (5) from the activation of oxidative cascades such as NADP (H) oxidase, peroxynitrites, or superoxide dismutase (SOD). However, the effects of hyperglycemia are more erratic: moderate hyperglycemia is sufficient to induce adverse structural changes in the mesenteric vasculature, but more severe hyperglycemia is essential to cause endothelial dysfunction.

It is more interesting that the blocking of these pathways has significant effects on the activation/deactivation of vascular remodeling, independent of the correction or not, of hyperinsulinism or insulin resistance. This shows that intracellular cascades, in most of these mechanisms, have no feedback from insulin or glucose receptors.

On the other hand, it is likely that the vascular remodeling associated with insulin resistance, due to the stimulation of growth factors, from the pathways, is due to changes in vascular hemodynamics or to the increase in peripheral resistances, as in the case of arterial hypertension.

The new drugs, which modify the inflammatory modulating response, such as tocilizumab (anti-IL-6R alpha) and canakinumab (anti-IL-1b), will be drugs that could further modify the cardiovascular risk of these patients in the future, since it could modify the vascular inflammatory microenvironment, preventing vascular modeling and the subsequent formation of atheromatous plaques. Another pharmacological group that has gained importance in recent years is LCZ696, which, as several clinical studies have shown, modifies the cardiovascular morbidity and mortality of one of the most frequent pathologies of clinical practice, heart failure. However, new studies show that it is capable of producing effects in vascular repair, increasing the CPE at the vascular level, and avoiding vascular remodeling, even in experimental models with insulin resistance.

The concept of remodeling and vascular inflammation, which a decade ago was only important at the level of basic research, step-by-step has proven crucial in the appearance of atherosclerosis, called subclinical atherosclerosis. Much progress has been made in the treatment and discovery of pathophysiological mechanisms, rest improve the studies of deterrence, and its correlation with the reduction of cardiovascular risk; this is, perhaps, the decade in which we can advance in this.
