Oh Kei Shing, Febres-Aldana Christopher A, Kuritzky Nicholas, Ujueta Francisco, Arenas Ivan A, Sriganeshan Vathany, Medina Ana Maria, Poppiti Robert
Arkadi M. Rywlin, MD Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL, USA.
Arkadi M. Rywlin, MD Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL, USA.
Cardiovasc Pathol. 2021 May-Jun;52:107318. doi: 10.1016/j.carpath.2021.107318. Epub 2021 Jan 12.
Fibrosis, calcification, and ossification are histopathologic hallmarks of calcific aortic valve disease (CAVD), a leading cause of morbidity and mortality in the aging population. Cellular senescence contributes to a functional decay in chronic diseases by intensifying tissue remodeling and impairing tissue regeneration. We evaluated the expression of P16 and P53 as surrogate markers of senescence in CAVD.
Aortic valves from 27 individuals with severe CAVD requiring aortic valve replacement were selected for routine histologic processing. Immunohistochemical expression of P16 and P53 was quantified using computerized image analysis on fields matching compartments with varying degrees of tissue remodeling.
All aortic valves demonstrated P16 and P53-positive cells. The percentage of P16 -positive cells, but not of P53, was higher in areas of calcification and/or ossification (57.21%±26.31, n=40) and severe fibrosis (54.79%±27.19, n=25) than in areas with minimal to mild tissue remodeling (13.69% ± 11.88, n=16, P<.0001). P16 expression was observed in interstitial valve cells within all compartments proportional to the degree of fibrosis and did not correlate with age, severity of aortic stenosis, or P53 expression. Multiple linear regression analysis by backward elimination revealed P16 expression was lower among statin users (P<.01).
P16- expression is ubiquitous in calcified aortic valves and correlates with severity of tissue remodeling, suggesting a role of cellular senescence in the progression of CAVD. Further research is needed to identify possible treatment modalities as disease modifying agents for CAVD.
纤维化、钙化和骨化是钙化性主动脉瓣疾病（CAVD）的组织病理学特征，CAVD是老年人群发病和死亡的主要原因。细胞衰老通过加剧组织重塑和损害组织再生导致慢性疾病功能衰退。我们评估了P16和P53作为CAVD衰老替代标志物的表达。
选取27例因严重CAVD需要进行主动脉瓣置换的患者的主动脉瓣进行常规组织学处理。使用计算机图像分析对与不同程度组织重塑区域相匹配的视野进行P16和P53免疫组化表达定量。
所有主动脉瓣均显示P16和P53阳性细胞。钙化和/或骨化区域（57.21%±26.31，n = 40）和严重纤维化区域（54.79%±27.19，n = 25）的P16阳性细胞百分比高于轻度至中度组织重塑区域（13.69% ± 11.88，n = 16，P <.0001），而P53阳性细胞百分比则无差异。在所有区域的间质瓣膜细胞中均观察到P16表达，其与纤维化程度成正比，与年龄、主动脉狭窄严重程度或P53表达无关。通过向后排除法进行的多元线性回归分析显示，他汀类药物使用者的P16表达较低（P <.01）。
P16表达在钙化主动脉瓣中普遍存在，且与组织重塑严重程度相关，提示细胞衰老在CAVD进展中起作用。需要进一步研究以确定可能作为CAVD疾病修饰剂的治疗方式。
