2. Academic Validation
  3. NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension

NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension

  • Signal Transduct Target Ther. 2023 Sep 18;8(1):353. doi: 10.1038/s41392-023-01577-3.
Yumin Qiu # 1 2 3,  Shiyue Xu # 1 2 3,  Xi Chen # 1 2 3,  Xing Wu # 1 2 3,  Zhe Zhou 1 2 3,  Jianning Zhang 1 2 3,  Qiang Tu 1 2 3,  Bing Dong 1 2 3,  Zhefu Liu 1 2 3,  Jiang He 1 2 3,  Xiaoyu Zhang 1 2 3,  Shuangshuang Liu 1 2 3,  Chen Su 1 2 3,  Hui Huang 4,  Wenhao Xia 5 6 7 8,  Jun Tao 9 10 11
Affiliations

Affiliations

  • 1 Department of Hypertension and Vascular Disease, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China.
  • 2 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, 510080, Guangzhou, China.
  • 3 Key Laboratory on Assisted Circulation, Ministry of Health, 510080, Guangzhou, China.
  • 4 Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-sen University, 518033, Shenzhen, China. huangh8@mail.sysu.edu.cn.
  • 5 Department of Hypertension and Vascular Disease, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China. xwhzsyy@163.com.
  • 6 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, 510080, Guangzhou, China. xwhzsyy@163.com.
  • 7 Key Laboratory on Assisted Circulation, Ministry of Health, 510080, Guangzhou, China. xwhzsyy@163.com.
  • 8 Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, 530022, Nanning, China. xwhzsyy@163.com.
  • 9 Department of Hypertension and Vascular Disease, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China. taojungz123@163.com.
  • 10 National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, 510080, Guangzhou, China. taojungz123@163.com.
  • 11 Key Laboratory on Assisted Circulation, Ministry of Health, 510080, Guangzhou, China. taojungz123@163.com.
  • # Contributed equally.
PMID: 37718359 DOI: 10.1038/s41392-023-01577-3
Abstract

Hypertension is characterized by endothelial dysfunction and arterial stiffness, which contribute to the pathogenesis of atherosclerotic cardiovascular diseases. Nicotinamide adenine dinucleotide (NAD+) is an indispensable cofactor in all living cells that is involved in fundamental biological processes. However, in hypertensive patients, alterations in NAD+ levels and their relation with blood pressure (BP) elevation and vascular damage have not yet been studied. Here we reported that hypertensive patients exhibited lower NAD+ levels, as detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS), in both peripheral blood mononuclear cells (PBMCs) and aortas, which was parallel to vascular dysfunction. NAD+ boosting therapy with nicotinamide mononucleotide (NMN) supplement reduced BP and ameliorated vascular dysfunction in hypertensive patients (NCT04903210) and AngII-induced hypertensive mice. Upregulation of CD38 in endothelial cells led to endothelial NAD+ exhaustion by reducing NMN bioavailability. Pro-inflammatory macrophages infiltration and increase in IL-1β generation derived from pro-inflammatory macrophages resulted in higher CD38 expression by activating JAK1-STAT1 signaling pathway. CD38 KO, CD38 inhibitors treatment, or adeno-associated virus (AAV)-mediated endothelial CD38 knockdown lowered BP and improved vascular dysfunction in AngII-induced hypertensive mice. The present study demonstrated for the first time that endothelial CD38 activation and subsequently accelerated NAD+ degradation due to enhanced macrophage-derived IL-1β production was responsible for BP elevation and vascular damage in hypertension. NAD+ boosting therapy can be used as a novel therapeutic strategy for the management of hypertensive patients.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z