Like patients with SLE, a strong gender bias exists in NZBWF1 mice and multiple genetic mutations contribute to the development of SLE. components leads to a breach of immunological tolerance, and that this loss of tolerance results in the production of autoantibodies, most often to self-molecules in the nucleus, cytoplasm and on the cell Mepenzolate Bromide surface. Antinuclear antibodies are found in ~95% of SLE patients and anti-dsDNA antibodies have been detected in 70% of patients [Reveille, 2004]. The presence of autoantibodies leads to the formation of immune complexes, which can deposit in virtually any tissue in the body. The classification criteria for SLE, as recently revised and validated by the Systemic Lupus International Collaborating Clinics (SLICC) in 2012, are outlined in Table 1. A person is diagnosed with SLE if they have had 4 or more of the 17 criteria outlined, including at least 1 clinical criterion and 1 immunological criterion; alternatively a patient can be diagnosed with biopsy-proven lupus nephritis and positive antinuclear or anti-dsDNA antibodies [Petri 2012]. Table 1. Systemic Lupus International Collaborating Clinics (SLICC) criteria for the classification of SLE. 1997]. The bimodal pattern of mortality in SLE was first described by Urowitz and colleagues in the Toronto lupus cohort: those who die in the first year after diagnosis have active lupus, and those who die later in the course of the disease have inactive lupus and a high incidence of atherosclerosis and myocardial infarction [Urowitz 1976]. This bimodal pattern, as well as the high incidence of death due to cardiovascular disease, has been confirmed in subsequent studies [Mody 1994; Abu-Shakra 1995; Bernatsky 2006]. In addition, women with SLE aged 35C44 were 50 times more likely to have a cardiac event (myocardial infarction or angina pectoris) compared with age-matched controls participating in the Framingham Offspring Study [Manzi 1997]. Hypertension is an important, yet understudied, cardiovascular risk factor that is prevalent in this patient population. This review will discuss both clinical and experimental evidence for the increased prevalence of hypertension and potential underlying mechanisms. Hypertension in SLE Hypertension is a major risk factor for the development of cardiovascular disease and is prevalent in patients with SLE [Budman and Steinberg, 1976; Mandell, 1987; Petri, 2000; Selzer 2001; Al-Herz 2003; Sabio 2011; Shaharir 2015]. The incidence of hypertension is especially striking in women younger than 40: in one cohort 40% of women under 40 were hypertensive compared with 11% of the control subjects [Sabio 2011]. While the pathogenesis of hypertension in SLE is not fully understood [Ryan, 2009], a combination of traditional (age, sex, obesity, ethnicity) and disease-related factors (immune system dysfunction, inflammation, renal involvement, drug side effects) may contribute to hypertension in SLE patients [Sabio 2001; Chaiamnuay 2007]. Specifically, renal function, the reninCangiotensin system (RAS), sex hormones, inflammatory cytokines, and autoantibodies will be discussed in this review. Mepenzolate Bromide Renal PIK3C2G function In ~50% of SLE patients, the kidneys are affected in the form of immune complex glomerulonephritis, and nearly all patients show evidence of kidney injury on biopsy [Boumpas 1995; Guo 2010]; Mepenzolate Bromide however, SLE-associated hypertension can occur independently of nephritis [Ward and Studenski, 1992; Petrin 1993]. For example, a recent study by Shaharir and colleagues revealed that 53% of SLE patients in one cohort were hypertensive despite the absence of nephritis [Shaharir 2015]. Because of the importance of the kidney in the long-term control of blood pressure, impaired renal function is certain to contribute to Mepenzolate Bromide the prevalent hypertension in SLE patients. Impaired renal hemodynamics and tubular function are likely contributors, since the ability of the kidney to excrete sodium and water.