Ronald L Dalman, MD, Walter Clifford Chidester and Elsa Rooney Chidester Professor, Chief, Division of Vascular Surgery, Department Surgery, Stanford University School of Medicine
Research Description: Our group has focused on the fundamental pathogenesis, pharmacological intervention and risk factors of abdominal aortic aneurysm (AAA) disease over two decades. Although diabetes worsens most cardiovascular diseases such as atherosclerosis, it is the sole clinical condition that lowers the risk for, and also limits the progression of existing small, AAAs. The mechanisms through which diabetes alters AAA formation and progression have not been defined. In the mouse model of type 1 diabetes, we have demonstrated the diabetes-mediated attenuation of abdominal aortic aneurysms and its phenotype restoration by normalizing hyperglycemia via insulin administration. Very recently, we found that the anti-hyperglycemic drug metformin suppressed experimental AAA progression and that clinical aneurysms progressed more slowly in diabetic aneurysm patients than in the patients not taking metformin. Currently, we are exploring the cellular and molecular mechanisms by which the dysfunctions of angiogenesis, innate and adaptive immunity in diabetic conditions contribute to aneurysm inhibition. Our group has collaborations with several investigators in the Stanford Diabetes Research Center as described below.
Selected relevant publications (Stanford DRC Members in BOLD):
1. Fujimura N, Xiong J, Kettler EB, Xuan H, Glover KJ, Mell MW, Xu B & Dalman RL. Metformin treatment status and abdominal aortic aneurysm disease progression. J Vasc Surg 64:46-54, 2016.
2. Fujimura N, Xu B, Dalman J, Deng H, Aoyama K & Dalman RL. CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow. Sci Rep 5:11664, 2015.
3. Rouer M, Xu BH, Xuan HJ, Tanaka H, Fujimura N, Glover KJ, Furusho Y, Gerritsen M & Dalman RL. Rapamycin limits the growth of established experimental abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 47:493-500, 2014.
4. Iida Y, Xu B, Xuan H, Glover KJ, Tanaka H, Hu X, Fujimura N, Wang W, Schultz JR, Turner CR & Dalman RL. Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression. Arterioscler Thromb Vasc Biol 33:718-726, 2013.
5. Iida Y, Xu B, Schultz GM, Chow V, White JJ, Sulaimon S, Hezi-Yamit A, Peterson SR & Dalman RL. Efficacy and mechanism of angiotensin II receptor blocker treatment in experimental abdominal aortic aneurysms. PLoS One. 7:e49642, 2012.
6. Miyama N, Dua MM, Yeung JJ, Schultz GM, Asagami T, Sho E, Sho M & Dalman RL. Hyperglycemia limits experimental aortic aneurysm progression. J Vasc Surg 252:975-983, 2010.
7. Dua MM, Miyama N, Azuma J, Schultz GM, Sho M, Morser J & Dalman RL. Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease. Surgery 148:429-35, 2010.
8. Tedesco MM, Terashima M, Blankenberg FG, Levashova Z, Spin JM, Backer MV, Backer JM, Sho M, Sho E, McConnell MV & Dalman RL. Analysis of in situ and ex vivo vascular endothelial growth factor receptor expression during experimental aortic aneurysm progression. Arterioscler Thromb Vasc Biol. 29:1452-157, 2009.
9. Maegdefessel L, Azuma J, Toh R, Deng A, Merk DR, Raiesdana A, Leeper NJ, Raaz U, Schoelmerich AM, McConnell MV, Dalman RL, Spin JM, Tsao PS. MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med 2012; 4: 122ra22.