The role of macrophages in hypertension and its complications

Abstract

Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent disease associated with catastrophic cardiovascular morbidity. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines induce endothelial and epithelial dysfunction, respectively, resulting in vascular oxidative stress and impairment of sodium excretion. By contrast, VEGF-C-expressing macrophages in the skin can facilitate the removal of excess interstitial stores of sodium by stimulating lymphangiogenesis. Inappropriate activation of the renin-angiotensin system (RAS) contributes to essential hypertension in a majority of patients, and macrophages express the type 1 (AT1) receptor for angiotensin II (Ang II). While proinflammatory macrophages clearly contribute to RAS-dependent hypertension, activation of the AT1 receptor directly on macrophages suppresses their M1 polarization and limits tubular and interstitial damage to the kidney during hypertension. Thus, stimulating the macrophage AT1 receptor ameliorates the target organ damage and immune stimulation provoked by AT1 receptor activation in intrinsic renal and vascular cells. The proinflammatory cytokines TNF-α and IL-1β produced by M1 macrophages drive blood pressure elevation and consequent target organ damage. However, additional studies are needed to identify the tissues in which these cytokines act and the signaling pathways they stimulate during hypertension. Moreover, identifying the precise myeloid cell subsets that contribute to hypertension should guide the development of more precise immunomodulatory therapies for patients with persistent blood pressure elevation and progressive end-organ injury.

VEGF‐C attenuates renal damage in salt‐sensitive hypertension

“…Second, we sought to evaluate the effect of VEGF‐C on renal oxidative stress induced by high salt. An important contributor to the pathogenesis of hypertension is oxidative stress (Harrison & Gongora, ; Justin Rucker & Crowley, ; Touyz & Briones, ). High salt has been shown to increase the production of reactive oxygen species leading to impaired nitric oxide signaling, arterial stiffening, and vasoconstriction (Banday, Muhammad, Fazili, & Lokhandwala, ; Bayorh, Ganafa, Socci, Silvestrov, & Abukhalaf, ; Dobrian et al, ; Trolliet, Rudd, & Loscalzo, ).…”

The effect of short-term perindopril and telmisartan treatment on circulating levels of anti-inflammatory cytokines in hypertensive patients

“…Both innate and adaptive immune responses seem to play an important role in the pathogenesis of hypertension [4]. Through the generation of inflammatory cytokines and reactive oxygen species, macrophages can directly impair vasculature endothelial and smooth muscle function, leading to vasoconstriction and resultant hypertension [5]. In turn, imbalance of distinct functions of T-cell subsets could be an initiating event in the pathogenesis of hypertension [6].…”

The Caspase Inhibitor Z-VAD-FMK Alleviates Endotoxic Shock via Inducing Macrophages Necroptosis and Promoting MDSCs-Mediated Inhibition of Macrophages Activation

“…As is known, macrophages play a key role in the pathogenesis of endotoxic shock by producing large amounts of inflammatory cytokines and NO (6)(7)(8). We guess that the different treatment effect of i.p.…”

“…In the early stages of endotoxin shock, hyper-activated macrophages can drive tissue damage by producing excessive amounts of pro-inflammatory cytokines. After stimulation with bacterial lipopolysaccharide (LPS), macrophages can differentiate into classically macrophages (M1) that can secrete pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-12, and produce nitric oxide (NO) (6)(7)(8)(9)(10)(11). In the early stages of endotoxin shock, LPS can bind TLR4 and trigger MyD88-and TRIF-dependent expression of pro-inflammatory cytokines and type I interferons (12)(13)(14).…”