Thymosin β4 Deficiency Exacerbates Renal and Cardiac Injury in Angiotensin-II-Induced Hypertension.
Thymosin β4 Deficiency Exacerbates Renal and Cardiac Injury in Angiotensin-II-Induced Hypertension.
复制标题
DOI：
10.1161/hypertensionaha.118.10952
复制
发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Carretero OA
中科院分区：
文献类型：
--
作者：
Kumar N;Liao TD;Romero CA;Maheshwari M;Peterson EL;Carretero OA
Thymosin β4 (Tβ4), a ubiquitous peptide, regulates several cellular processes that include cell morphology, wound healing and inflammatory response. Administration of exogenous Tβ4 is protective in diabetic nephropathy and in a unilateral ureteral obstruction model. However, the role of endogenous Tβ4 in health and disease conditions remains unclear. To elucidate the pathophysiological role of endogenous Tβ4 in hypertension, we examined angiotensin-II (Ang-II)-induced renal and cardiac damage in Tβ4 knockout (Tβ4 KO) mice. Tβ4 KO and wild-type (WT) C57BL/6 mice were infused continuously for six weeks with either vehicle or Ang-II (980 ng/kg/min). At baseline, Tβ4 deficiency did not affect renal and cardiac function. Systolic blood pressure (SBP) in the Ang-II group was similar in WT and Tβ4 KO mice (WT Ang-II 179.25±10.11 mmHg; Tβ4 KO Ang-II 169.81±6.54 mmHg). Despite the similar SBP following Ang-II infusion, Tβ4-deficient mice had dramatically increased albuminuria and decreased nephrin expression in the kidney (P<0.005). In the heart of Tβ4 KO mice, Ang-II reduced ejection fraction (EF) and shortening fraction (EF: WT Ang-II 77.95±1.03%; Tβ4 KO Ang-II 62.58±3.25%; P<0.005), which was accompanied by cardiac hypertrophy and left ventricular dilatation. Additionally, renal and cardiac infiltration of CD68 macrophages, intercellular adhesion molecule-1 (ICAM-1) and total collagen content were increased after Ang-II infusion in Tβ4 KO mice (P<0.005). Overall, our data indicate that endogenous Tβ4 is crucial in preventing tissue injury from Ang-II-induced hypertension. This study gives new insights into the protective role of endogenous Tβ4 in hypertensive end-organ damage.
