LOX-1 dependent overexpression of immunoglobulins in cardiomyocytes in response to angiotensin II

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• 作者：Bum-Yong Kang ; Changping Hu ; Sastry Prayaga ; Magomed Khaidakov ; Tatsuya Sawamura ; Ki-Bae Seung ; Jawahar L. Mehta
• 关键词：Angiotensin II ; Immunoglobulin ; LOX-1 ; Microarray
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：6 February 2009
• 年：2009
• 卷：379
• 期：2
• 页码：395-399
• 全文大小：277 K

文摘

LOX-1, a cell surface lectin-like receptor, is upregulated by oxidized low-density lipoprotein (ox-LDL) and angiotensin II (Ang II), and plays an important role in host defense. The specific C-type lectin domain on LOX-1 is essential for ox-LDL binding and internalization, generation of oxidant species and eliciting immune response. Here, we show that LOX-1 deletion alters genes that relate to immune response. Microarray (and qPCR) analysis of cardiac tissues showed downregulated expression of several immunoglobulins (Igk-V8, Igk-C, Igh-6, Igj, Ighg, Igh, and Igl-V1) in the LOX-1 knockout (KO) mice [p < 0.05 vs. the wild-type (WT) mice]. The expression of these immunoglobulins was upregulated several-fold in the LOX-1 KO mice hearts when these mice were infused with Ang II (p < 0.05, vs. WT mice). Importantly, cultured mouse HL-1 cardiomyocytes expressed these immunoglobulins, and pretreatment of cardiomyocytes with a specific anti-LOX-1 antibody enhanced the generation of immunoglobulins upon subsequent exposure to Ang II. These observations mirrored the data obtained from WT and LOX-1 KO mice hearts in the resting state and following Ang II infusion. This study provides first set of data on immunoglobulin expression in cardiac tissues of WT and LOX-1 KO mice and in cultured HL-1 cardiomyocytes, and demonstrates that LOX-1 inactivation leads to upregulation of immunoglobulins in cardiomyocytes upon challenge with Ang II.