PS-B06-6: LOSS OF SKELETAL MUSCLE MASS INFLUENCES IMMUNE HOMEOSTASIS AND ACCELERATES THE RENAL-RELATED RISK OF HYPERTENSION. (January 2023)

• Record Type: Journal Article
• Authors: Mogi, Masaki; Liu, Shuang; Kiyoi, Takeshi
• Is Part Of: Journal of hypertension. Volume 41(2023)Supplement 1
• Page Start: e368
• Publication Date: 2023-01
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000916548.43619.70
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Patients with systemic lupus erythematosus (SLE) are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. Also, SLE related autoimmune renal diseases are in part imputed to classical vascular risk factors such as hypertension. The relationship between circulating autoantibodies and hypertension has been recognized. How sarcopenia hastens immune dysfunction in SLE and autoimmunity per se is an underlying cause of hypertension remains uncertain. The present study elucidated the relationship between skeletal muscle loss and systemic immune status with regards to how sarcopenia-mediated immune dysfunction contributes as a critical risk factor in hypertension. Design and Methods: A denervation-induced skeletal muscle loss model was established, and the function of the immune system was evaluated. Systemic immune cell proportions and serum cytokine levels were profiled. Calcium influx and mitochondrial function were also assessed in the T cells. Finally, MRL/lpr mice were used to assess the influence of denervation-induced sarcopenia on SLE-related lupus nephritis progression and circulating autoantibodies, along with the cytokines that contributes to the development of hypertension, such as TNF-α and MCP-1, were evaluated. Results: The results of immune status profiling and functional assessment demonstrated that the loss of skeletal muscle shifts the immune balance in favor of the Th1/Th17 axis. Along with the peak Ca2+ influx, denervation-induced amyotrophy also impaired the spare respiratory capacity in mitochondrial of T cells, as well as the basal respiration and adenosine triphosphate production. The results of proteinuria tracing, serum blood urea nitrogen level, and C3 and IgE deposition in mesangium and capsular adhesion suggests that the sarcopenia promoted nephritis progression. A significant increase of the level in TNF-α, which promotes renal vasoconstriction, a pro-hypertensive effect, was also observed in sarcopenic mice. Conclusion: Consequently, sarcopenia might promote the progression of lupus nephritis because of the enhancement of systemic Th1/Th17 functions and accelerate the deposition of the vascular damage factors. The data herein suggested that the protection from developing hypertension in SLE patient may afforded by preventing skeletal muscle losing. A multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia in the management of SLE-related hypertension.