Plenary Session 8

3月27日［土］11:00-12:30

 
  Molecular mechanisms of cardiovascular aging and diseases progression
  
 
   
  動脈硬化や糖尿病、心不全など多くの心血管代謝疾患は、加齢とともにその発症が増加する。加齢に伴って惹起される慢性炎症（Inflammaging）が、心血管代謝疾患を含めた様々な加齢関連疾患の発症・進展に関与すると想定されている。例えば、動脈硬化の発症・進展には、高コレステロール血症を基盤とした血管の慢性炎症が重要であることは、スタチンを用いた多くの基礎・臨床研究で示されているが、CANTOS研究ではさらなる炎症制御を行うことで、残余リスクを低下させうることが示されている。また、肥満や加齢に伴う内臓脂肪の慢性炎症が全身性のインスリン抵抗性を惹起することで、心血管系の機能を負に制御しうることが示されている。さらに、心不全の病態においても、心筋細胞や非心筋細胞における加齢性炎症形質が、その発症・進展に関与することが示唆されている。これらの加齢性慢性炎症の機序には、クローン性血球増殖や腸内細菌叢の異常、老化細胞の蓄積、異常な免疫系の反応など、様々な病的老化形質の関与が示唆されているが、全貌は明らかでない。また、これら加齢性慢性炎症を標的とした心血管代謝疾患に対する治療法の開発も発展途上である。そこで本セッションでは、加齢性慢性炎症による心血管代謝疾患制御に関して、現状と今後の展望について議論することで、加齢によって増加する心血管代謝疾患に対する新たな治療ストラテジーの開発に繋げたい。
The incidence of cardiovascular and metabolic diseases, such as atherosclerosis, diabetes, and heart failure, increases with age. It has been suggested that an age-associated increase in chronic inflammation (inflammaging) contributes to the onset and progression of age-related diseases including cardiovascular and metabolic diseases. For example, a number of basic and clinical studies with statins have shown that age-associated hypercholesterolemia promotes vascular inflammation, thereby leading to the onset and progression of atherosclerosis. The CANTOS study demonstrated that direct suppression of the inflammatory response can lead to a reduction of residual cardiovascular risk. Age and/or obesity-induced visceral adipose tissue inflammation provokes systemic insulin resistance, which negatively regulates cardiovascular function. It has also been reported that inflammaging in the heart is involved in the onset and progression of heart failure. The mechanisms associated with inflammaging include: age-associated clonal hematopoiesis; dysbiosis; accumulation of senescent cells, and abnormal immune response, however the entirety of the mechanisms involved remain elusive. Moreover, the therapeutic strategy targeting inflammaging for cardiovascular and metabolic diseases has not yet been sufficiently developed. In the present session we will review the issues surrounding inflammaging in cardiovascular and metabolic diseases, and discuss a perspective of novel therapeutic strategies of immune modulation.
 
 
   
 
 
Tohru Minamino   Tohru Minamino
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo
   Kenneth Walsh   Kenneth Walsh
University of Virginia School of Medicine, Charlottesville, USA
 
 
 
 
   
 
 
Kenneth Walsh   Kenneth Walsh
University of Virginia School of Medicine, Charlottesville, USA
   Koya Ozawa   Koya Ozawa
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, USA
 
 
 
Daiju Fukuda   Daiju Fukuda
Department of Cardio-Diabetes Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima
   Ichiro Manabe   Ichiro Manabe
Department of Disease Biology and Molecular Medicine, Chiba University Graduate School of Medicine, Chiba
 
 
 
Yumiko Oishi   Yumiko Oishi
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo
   Masayoshi Suda   Masayoshi Suda
Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata