Hyperuricemia and Endothelial Function: Is It a Simple Association or Do Gender Differences Play a Role in This Binomial?

Abstract

The endothelium plays a fundamental role in the biological processes that ensure physiological vessel integrity, synthesizing numerous substances that are capable of modulating the tone of vessels, inflammation and the immune system, and platelet function. Endothelial dysfunction refers to an anomaly that develops at the level of the tunica that lines the internal surface of arterial and venous vessels, or, more precisely, an alteration to normal endothelial function, which involves the loss of some structural and/or functional characteristics. Studies on sex differences in endothelial function are conflicting, with some showing an earlier decline in endothelial function in men compared to women, while others show a similar age of onset between the sexes. Since increased cardiovascular risk coincides with menopause, female hormones, particularly estrogen, are generally believed to be cardioprotective. Furthermore, it is often proposed that androgens are harmful. In truth, these relationships are more complex than one might think and are not just dependent on fluctuations in circulating hormones. An increase in serum uric acid is widely regarded as a possible risk factor for cardiovascular disease; however, its role in the occurrence of endothelial dysfunction has not yet been elucidated. Several studies in the literature have evaluated sex-related differences in the association between elevated uric acid levels and cardiovascular events, with conflicting results. The association between uric acid and cardiovascular disease is still controversial, and it is not yet clear how gender differences affect the serum concentration of these substances. This review was primarily aimed at clarifying the effects of uric acid at the level of the vascular endothelium and describing how it could theoretically cause damage to endothelial integrity. The second aim was to determine if there are gender differences in uric acid metabolism and how these differences interact with the vascular endothelium.

Hyperuricemia: A key contributor to endothelial dysfunction in cardiovascular diseases

“…To date, the majority of the literature indicates that HUA contributes to ED, although the findings are contradictory, possibly due to the cohorts of study subjects differing in age, race, sex, and treatment regimens 114,115 . Recently, a cross‐sectional and retrospective study suggested independent association between HUA and hypertension only in men younger than 60 years of age 30 .…”

“…To date, the majority of the literature indicates that HUA contributes to ED, although the findings are contradictory, possibly due to the cohorts of study subjects differing in age, race, sex, and treatment regimens. 114,115 Recently, a cross-sectional and retrospective study suggested independent association between HUA and hypertension only in men younger than 60 years of age. 30 However, a meta-analysis including 18 prospective cohorts demonstrated an association between HUA and a high risk of incident hypertension in young individuals T A B L E 1 Mechanism of action involved in pharmacologic interventions for hyperuricemia-induced endothelial dysfunction.…”

Endothelial dysfunction, platelet hyperactivity, hypertension, and the metabolic syndrome: molecular insights and combating strategies

“…Several clinical circumstances involve the oxidation of tetrahydrobiopterin (BH4) and mitochondrial electron transport, as well as the inactivation of nicotinamide-adenine dinucleotide phosphate (74). Endothelial dysfunction is related to oxidative stress in cardiovascular disorders such as CAD and stroke (75). Renovascular hypertension, for example, is produced by constriction of the blood vessels, which activates the renin-angiotensin system and raises the synthesis of angiotensin II (Ang II), the system's main active peptide, thus increasing ROS (76).…”

“…Remodeling, platelet aggregation, vasodilation loss, inflammation, and smooth muscle cell proliferation may occur from this imbalance ( 74 ). Endothelial dysfunction is related to oxidative stress in cardiovascular disorders such as CAD and stroke ( 75 ). Renovascular hypertension, for example, is produced by constriction of the blood vessels, which activates the renin-angiotensin system and raises the synthesis of angiotensin II (Ang II), the system’s main active peptide, thus increasing ROS ( 76 ).…”

Vitamin D: Can Gender Medicine Have a Role?

“…Conception, implantation, and early pregnancy development, as well as placental development, require energy and micronutrients, including B complex vitamins, vitamins A and D, and folic acid. It should be emphasized that some categories of women are more at risk of nutritional deficiencies [ 14 , 15 ]. Obese women, for example, have an increased risk of vitamin D deficiency; smokers often have lower levels of omega-3 fatty acids in their breast milk, and women who follow a vegetarian/vegan diet instead are exposed to a greater risk of vitamin D deficiency, lack of vitamins B12 and D, and calcium [ 14 , 15 ].…”