Most hypertensive cases are primary and heavily associated with modifiable risk factors like salt intake. Evidence suggests that even small reductions in salt consumption reduce blood pressure in all age groups. In that regard, the ACC/AHA described a distinct set of individuals who exhibit salt-sensitivity, regardless of their hypertensive status. Data has shown that salt-sensitivity is an independent risk factor for cardiovascular events and mortality. However, despite extensive research, the pathogenesis of salt-sensitive hypertension is still unclear and tremendously challenged by its multifactorial etiology, complicated genetic influences, and the unavailability of a diagnostic tool. So far, the important roles of the renin-angiotensin-aldosterone system, sympathetic nervous system, and immune system in the pathogenesis of salt-sensitive hypertension have been studied. In the first part of this review, we focus on how the systems mentioned above are aberrantly regulated in salt-sensitive hypertension. We follow this with an emphasis on genetic variants in those systems that are associated with and/or increase predisposition to salt-sensitivity in humans.

Traumatic brain injury (TBI) remains a major cause of morbidity and disability worldwide and a healthcare burden. TBI is an important risk factor for neurodegenerative diseases hallmarked by exacerbated neuroinflammation. Neuroinflammation in the cerebral cortex plays a critical role in secondary injury progression following TBI. The NOD-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a key player in initiating the inflammatory response in various central nervous system disorders entailing TBI. This current study aims to investigate the role of NLRP3 in repetitive mild traumatic brain injury (rmTBI) and identify the potential neuroprotective effect of saffron extract in regulating the NLRP3 inflammasome. 24 hours following the final injury, rmTBI causes an upregulation in mRNA levels of NLRP3, caspase-1, the apoptosis-associated speck-like protein containing a CARD (ASC), nuclear factor kappa B (NF-κB), interleukin-1Beta (IL-1β), interleukin 18 (IL-18), nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase 1 (HMOX1). Protein levels of NLRP3, sirtuin 1 (SIRT1), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), and neuronal nuclei (Neu N) also increased after rmTBI. Administration of saffron alleviated the degree of TBI, as evidenced by reducing the neuronal damage, astrocyte, and microglial activation. Pretreatment with saffron inhibited the activation of NLRP3, caspase-1, and ASC concurrent to reduced production of the inflammatory cytokines IL-1β and IL-18. Additionally, saffron extract enhanced SIRT1 expression, NRF2, and HMOX1 upregulation. These results suggest that NLRP3 inflammasome activation and the subsequent inflammatory response in the mice cortex are involved in the process of rmTBI. Saffron blocked the inflammatory response and relieved TBI by activating detoxifying genes and inhibiting NLRP3 activation. The effect of saffron on the NLRP3 inflammasome may be SIRT1 and NF-κB dependent in the rmTBI model. Thus, brain injury biomarkers will help in identifying a potential therapeutic target in treating TBI-induced neurodegenerative diseases.

T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce IL-21 promote germinal center (GC) B cell responses, leading to Ig production. Here we investigate the role of IL-21 and Tfh cells in hypertension. In response to angiotensin II–induced (Ang II–induced) hypertension, T cell IL-21 production was increased, and Il21 ^–/– mice developed blunted hypertension, attenuated vascular end-organ damage, and decreased IL-17A and IFN-γ production. Tfh-like cells and GC B cells accumulated in the aorta, and plasma IgG1 was increased in hypertensive WT but not Il21 ^–/– mice. Furthermore, Tfh cell–deficient mice developed blunted hypertension and vascular hypertrophy in response to Ang II infusion. Importantly, IL-21 neutralization reduced BP and reversed endothelial dysfunction and vascular inflammation. Moreover, recombinant IL-21 impaired endothelium-dependent relaxation ex vivo and decreased NO production from cultured endothelial cells. Finally, we show in humans that peripheral blood T cell production of IL-21 correlated with systolic BP and IL-17A production. These data suggest that IL-21 may be a novel therapeutic target for the treatment of hypertension and its micro- and macrovascular complications.

According to the World Health Organization (WHO), an estimated 1.28 billion adults aged 30–79 years worldwide have hypertension; and every year, hypertension takes 7.6 million lives. High intakes of salt and sugar (mainly fructose from added sugars) have been linked to the etiology of hypertension, and this may be particularly true for countries undergoing the nutrition transition, such as Lebanon. Salt-induced hypertension and fructose-induced hypertension are manifested in different mechanisms, including Inflammation, aldosterone-mineralocorticoid receptor pathway, aldosterone independent mineralocorticoid receptor pathway, renin-angiotensin system (RAS), sympathetic nervous system (SNS) activity, and genetic mechanisms. This review describes the evolution of hypertension and cardiovascular diseases (CVDs) in Lebanon and aims to elucidate potential mechanisms where salt and fructose work together to induce hypertension. These mechanisms increase salt absorption, decrease salt excretion, induce endogenous fructose production, activate fructose-insulin-salt interaction, and trigger oxidative stress, thus leading to hypertension. The review also provides an up-to-date appraisal of current intake levels of salt and fructose in Lebanon and their main food contributors. It identifies ongoing salt and sugar intake reduction strategies in Lebanon while acknowledging the country’s limited scope of regulation and legislation. Finally, the review concludes with proposed public health strategies and suggestions for future research, which can reduce the intake levels of salt and fructose levels and contribute to curbing the CVD epidemic in the country.

Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play a role in hypertension by infiltrating target organs and releasing proinflammatory cytokines. We tested the hypothesis that the role of T cell SGK1 extends to memory T cells. We employed mice with a T cell deletion of SGK1, SGK1^fl/fl × tgCD4^cre mice, and used SGK1^fl/fl mice as controls. We treated the mice with L-NAME (0.5 mg/mL) for 2 weeks and allowed a 2-week washout interval, followed by a 3-week high-salt (HS) diet (4% NaCl). L-NAME/HS significantly increased blood pressure and memory T cell accumulation in the kidneys and bone marrow of SGK1^fl/fl mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1^fl/fl mice exhibited increased albuminuria, renal fibrosis, and interferon-γ levels after L-NAME/HS treatment. Myography demonstrated endothelial dysfunction in the mesenteric arterioles of SGK1^fl/fl mice. Bone marrow memory T cells were adoptively transferred from either mouse strain after L-NAME/HS administration to recipient CD45.1 mice fed the HS diet for 3 weeks. Only the mice that received cells from SGK1^fl/fl donors exhibited increased blood pressure and renal memory T cell infiltration. Our data suggest a new therapeutic target for decreasing hypertension-specific memory T cells and protecting against hypertension.