**1. Introduction**

Human immunodeficiency virus type 1 (HIV-1) infection is highly pathogenic since it stimulates a generalized immune activation involving not only the main targets of HIV-1 infection, such as CD4<sup>+</sup> T cells and monocytes/macrophages, but also cells that are not sensitive to viral infection.

Endothelial cells (ECs) are not fully permissive to HIV-1 infection, and there are no in vivo evidences that demonstrate the presence of replicating virus in ECs. Nowadays, the number of HIV-1-seropositive (HIV<sup>+</sup> ) patients that exhibit EC dysfunction is increasing vertiginously. In this chapter, the actual knowledges of how HIV-1 can directly and/or indirectly contribute to vascular dysfunction are reviewed. In particular, we underline the emerging role played by

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© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

some structural and regulatory HIV-1 proteins released in the microenvironment by infected cells in driving inflammation and EC dysregulation. This finding highlights the need to target these viral proteins for therapeutic benefit.

**2.2. Role of inflammatory cytokines and chemokines in the HIV-1-triggered** 

tion and migration of vascular smooth muscle cells [12].

levels are significantly upregulated in HIV<sup>+</sup>

such as IL-6 and M-CSF via a positive feedback loop.

ing to trans-endothelial migration of immune cells [16].

in the buildup of an atheromatous plaque [17].

of myocardial infarction in HIV<sup>+</sup>

positive feedback [17].

colony-stimulating factor (M-CSF) by T cells and monocytes [13].

Endothelial dysfunction and vascular diseases such as atherosclerosis and arterial damage are predominantly enhanced during a systemic chronic inflammatory status. Elevated levels of IL-6 have been associated with carotid atherosclerosis and progressive stenosis of the carotid artery, thereby upregulating the lipid uptake in macrophages and inhibiting the activity of lipoprotein lipase [10]. Increased carotid intima-media thickness (IMT) and hypertension are common features of patients with increased plasma levels of IL-18 [11], whereas TNF-α has a key role in promoting atherosclerosis, myocardial ischemia/reperfusion, and heart failure via several mechanisms: increased cholesterol uptake and foam cell formation in macrophages, augmented leukocyte transmigration in subendothelial structures, and increased prolifera-

HIV-1 infection generates a systemic chronic inflammatory disorder as a result of continuous alteration of the immune response, contributing to dyslipidemia, EC dysfunction, vascular smooth muscle cell proliferation and migration, and, ultimately, the atherosclerotic plaque formation. The virus itself promotes the release of IL-6, IL-18, and TNF-α, together with IFN-γ, IL-1β, IL-10, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and macrophage

Liver-synthesized C-reactive protein (CRP) is a member of the pentraxin family factors and is considered a marker for coronary vascular disease and endothelial damage. CRP plasma

lymphocyte count [14], and elevated CRP levels have been associated with an increased risk

IL-1, and TNF- α induce CRP, which in turn is able to activate pro-inflammatory cytokines

The levels of cell adhesion molecules such as vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are raised during HIV-1 infection, thus contribut-

HIV-1 causes a continuous recruitment of monocytes that migrate across the endothelial barrier in blood vessels, differentiate into macrophages, and produce pro-inflammatory cytokines, thus determining the progressive damage of vessel structures. Furthermore, HIV-1 replicates in macrophages and induces activation and synthesis of several pro-inflammatory cytokines that in turn induce endothelial activation and leukocyte adhesion generating a

likely relies on the upregulation of hepatic fatty acid synthesis and very low-density lipoprotein (VLDL) production, usually triggered by inflammatory cytokines as IFN-γ, TNF-α, and IL-1β [18]. At the same time, the continuous trans-endothelial migration of immune cells and their inhibited reverse transport determines the localization of monocytes inside the vessel wall and promotes the formation of foam cells, the fat-laden macrophages that are implicated

An important alteration in lipid metabolism is evident in more than 50% of HIV<sup>+</sup>

patients and inversely correlated with CD4<sup>+</sup>

Endothelial Cell Dysfunction in HIV-1 Infection http://dx.doi.org/10.5772/intechopen.73023

patients [15]. It is noteworthy that increased levels of IL-6,

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patients. It

**endothelial dysfunction**
