Influence of Klotho gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease

Abstract

Klotho protein has been associated with beneficial effects that contribute to the maintenance of cardiovascular health. Diverse studies suggest that alterations in the levels of this molecule may be associated with pathophysiological abnormalities that result in increased cardiovascular risk. The primary aim of this proof‐of‐concept study was to analyse the existence of a potential link between Klotho gene polymorphisms and the expression level of this gene in the vascular wall, and additionally with the incidence of cardiovascular disease and cardiovascular risk factors. Our results indicate that the variant G‐395A, located in the promoter region, influences Klotho gene vascular expression and is associated with the incidence of diabetes. Similarly, the exonic variant KL‐VS was associated with the incidence of atherosclerotic vascular disease and coronary artery disease. Moreover, vascular expression levels of Klotho were related with the incidence of diabetes mellitus and coronary artery disease. These findings, which need to be confirmed in larger studies, suggest a potential role of Klotho in the pathogenesis of vascular damage.

Circulating Klotho levels can predict long-term macrovascular outcomes in type 2 diabetic patients

“…The beneficial effects of Klotho have been associated with significant increases in the number of bcells, insulin storage levels in pancreatic islets, and glucosestimulated insulin secretion from pancreatic islets, all of which were shown to increase blood insulin levels in a diabetic mice model [33]. Several studies have reported the protective effects of Klotho in cardiovascular disease [16,34]. Klotho has been shown to modulate vascular tone via interactions between the renin-angiotensinaldosterone system (RAAS), nitric oxide production, and calcium and phosphate homeostasis [35,36].…”

Tissue expression and source of circulating αKlotho

“…Given the link between FGF23 and vascular complications in CKD, it is of principal interest to elucidate whether FGF23 modifies structural or functional properties of the vasculature via Klotho-dependent mechanisms. In aorta and in other arteries, Klotho mRNA is either not detected [40,52,65,[188][189][190] or detected at an extremely low level [1,16,[191][192][193][194][195][196][197][198][199]. This holds true also for vascular smooth muscle cells [15,189,196,[200][201][202][203][204] and endothelial cells [202,[205][206][207][208][209][210][211] when analyzed separately.…”

Nitride oxide synthase 3 and klotho gene polymorphisms in the pathogenesis of chronic kidney disease and age-related cognitive impairment: a systematic review and meta-analysis

“…In our current study, several limitations were noted. First, some factors that might influence NOS3 and klotho level including multiple sclerosis 95 , asthma 96 , chronic obstructive pulmonary disease 97 , and cardiovascular disease 5 were not controlled for. Second, due to relatively small sample size, our findings should be interpreted with caution, considering the potency for bias.…”