Heme- and iron-activated macrophages in sickle cell disease: an updated perspective.

Purpose Of Review: Sickle cell disease (SCD) is a hereditary blood disorder due to a single-point mutation in the β-globin gene. The ensuing hemoglobin has the tendency to polymerize upon deoxygenation, leading to the typical sickle shape of red blood cells. While the primary pathology of sickle cell disease is a direct consequence of altered red blood cells, emerging evidence highlights the central role of macrophages in mediating hemoglobin scavenging, perpetuating oxidative stress and inflammation, and causing endothelial dysfunction and tissue remodeling.

Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.

Introduction: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN.

Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of increasing M2 macrophages.

Salt-sensitive hypertension (SSHTN) is associated with M1 macrophage polarization and inflammatory responses, leading to inflammation-associated lymphangiogenesis and functional impairment across multiple organs, including kidneys and gonads. However, it remains unclear whether promoting M2 macrophage polarization can alleviate the hypertension, inflammation, and end organ damage in mice with salt sensitive hypertension (SSHTN). Male and female mice were made hypertensive by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.

Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of lowering blood pressure.

We reported that salt-sensitive hypertension (SSHTN) is associated with increased pro-inflammatory immune cells, inflammation, and inflammation-associated lymphangiogenesis in the kidneys and gonads of male and female mice. However, it is unknown whether these adverse end organ effects result from increased blood pressure (BP), elevated levels of salt, or both. We hypothesized that pharmaceutically lowering BP would not fully alleviate the renal and gonadal immune cell accumulation, inflammation, and lymphangiogenesis associated with SSHTN.

Unraveling Hypothalamus-Pituitary dysregulation: Hypergonadotropism in F progeny due to prenatal exposure to hexavalent chromium.

The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F rats. However, the mechanism driving hypergonadotropism in F rats exposed to Cr(VI) prenatally remains an enigma.

Indole Propionic Acid Increases T Regulatory Cells and Decreases T Helper 17 Cells and Blood Pressure in Mice with Salt-Sensitive Hypertension.

Hypertension affects over a billion adults worldwide and is a major risk factor for cardiovascular disease. Studies have reported that the microbiota and its metabolites regulate hypertension pathophysiology. Recently, tryptophan metabolites have been identified to contribute to and inhibit the progression of metabolic disorders and cardiovascular diseases, including hypertension.

Genetically inducing renal lymphangiogenesis attenuates hypertension in mice.

Background: Hypertension (HTN) is associated with renal proinflammatory immune cell infiltration and increased sodium retention. We reported previously that renal lymphatic vessels, which are responsible for trafficking immune cells from the interstitial space to draining lymph nodes, increase in density under hypertensive conditions. We also demonstrated that augmenting renal lymphatic density can prevent HTN in mice.

Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.

(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or indirect effect on lymphangiogenesis is unknown. We hypothesized that these 3 HTN stimuli directly increase lymphatic endothelial cell (LEC) proliferation, LEC 3-D matrix invasion and vessel formation, and sprouting of mouse mesometrial LVs.

Update on Immune Mechanisms in Hypertension.

The contribution of immune cells in the initiation and maintenance of hypertension is undeniable. Several studies have established the association between hypertension, inflammation, and immune cells from the innate and adaptive immune systems. Here, we provide an update to our 2017 American Journal of Hypertension review on the overview of the cellular immune responses involved in hypertension.

Hypertension induces gonadal macrophage imbalance, inflammation, lymphangiogenesis, and dysfunction.

Hypertension (HTN) is associated with gonadal dysfunction and impaired reproductive health in both men and women. An imbalance in the systemic and renal proinflammatory (M1)/anti-inflammatory (M2) macrophage ratio, increased inflammation, and inflammation-associated lymphangiogenesis have been observed in animals with HTN. However, the impact of HTN on gonadal macrophages, inflammation, and lymphatics remains obscure.

A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice.

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice.

Prenatal exposure to hexavalent chromium disrupts testicular steroidogenic pathway in peripubertal F rats.

We have reported sub-fertility in F progeny rats with gestational exposure to hexavalent chromium [Cr(VI)], which had disrupted Sertoli cell (SC) structure and function, and decreased testosterone (T). However, the underlying mechanism for reduced T remains to be understood. We tested the hypothesis "transient prenatal exposure to Cr(VI) affects testicular steroidogenesis by altering hormone receptors and steroidogenic enzyme proteins in Leydig cells (LCs).

Hypertension and reproductive dysfunction: a possible role of inflammation and inflammation-associated lymphangiogenesis in gonads.

Hypertension is one of the most prevalent diseases that leads to end organ damage especially affecting the heart, kidney, brain, and eyes. Numerous studies have evaluated the association between hypertension and impaired sexual health, in both men and women. The detrimental effects of hypertension in men includes erectile dysfunction, decrease in semen volume, sperm count and motility, and abnormal sperm morphology.

Prenatal exposure to excess chromium attenuates transcription factors regulating expression of androgen and follicle stimulating hormone receptors in Sertoli cells of prepuberal rats.

We have reported that gestational exposure to hexavalent chromium (CrVI) represses androgen receptor (Ar) and follicle stimulating hormone receptor (Fshr) in Sertoli cells (SCs) of adult rats, while the mechanism underlying remains obscure. We tested the hypothesis "transient gestational exposure to CrVI during the critical embryonic windows of testicular differentiation and growth may have adverse impact on transcription factors controlling the expression of Ar and Fshr in SCs of the F progeny". CrVI (KCrO) was given through drinking water (50 ppm, 100 ppm and 200 ppm), to pregnant rats from gestational day 9-14 (testicular differentiation) and 15 to 21 (prenatal differentiation and proliferation of SC); male progenies were sacrificed on postnatal day 30 (Completion of postnatal SC maturation).

Transient gestational exposure to drinking water containing excess hexavalent chromium modifies insulin signaling in liver and skeletal muscle of rat progeny.

Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure.

Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F progeny rats.

The effect of gestational exposure to CrVI (occupational/environmental pollutant and target to Sertoli cells(SC)) was tested in a rat model during the testicular differentiation from the bipotential gonad may interrupt spermatogenesis by disrupting SC tight junctions(TJ) and it's proteins and hormone receptors. Pregnant Wistar rats were exposed to 50/100/200ppm CrVI through drinking water during embryonic days 9-14. On Postnatal day 120, testes were subjected to ion exchange chromatographic analysis and revealed increased level of CrIII in SCs and germ cells, serum and testicular interstitial fluid(TIF).