Sirtuin 3 deficiency aggravates angiotensin II‐induced hypertensive cardiac injury by the impairment of lymphangiogenesis

Zhang, Chen; Li, Na; Suo, Mengying; Liu, Jing; Liu, Lingxin; Qi, Yan; Zheng, Xuehui; Xie, Lin; Hu, Yang; Bu, Peili

doi:10.1111/jcmm.16661

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…Sirtuin-3 overexpression or cotreatment with a VEGF-C variant, engineered for VEGFR-3 specificity, enhanced lymphangiogenesis, and decreased cardiac injury and fibrosis in Ang II-infused animals compared with controls. 98,99 VEGF-C also improved fluid clearance in the heart, reduced inflammation after 1 week, and decreased inflammation and BP, as confirmed by telemetry, after 4 weeks of treatment. 99 Salt-based models revealed similar findings.…”

Section: Lymphatics Of the Heart In Hypertensionmentioning

confidence: 59%

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

Rossitto,

Bertoldi,

Rutkowski

et al. 2024

Hypertension

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Blood pressure is regulated by vascular resistance and intravascular volume. However, exchanges of electrolytes and water between intra and extracellular spaces and filtration of fluid and solutes in the capillary beds blur the separation between intravascular and interstitial compartments. Contemporary paradigms of microvascular exchange posit filtration of fluids and solutes along the whole capillary bed and a prominent role of lymphatic vessels, rather than its venous end, for their reabsorption. In the last decade, these concepts have stimulated greater interest in and better understanding of the lymphatic system as one of the master regulators of interstitial volume homeostasis. Here, we describe the anatomy and function of the lymphatic system and focus on its plasticity in relation to the accumulation of interstitial sodium in hypertension. The pathophysiological relevance of the lymphatic system is exemplified in the kidneys, which are crucially involved in the control of blood pressure, but also hypertension-mediated cardiac damage. Preclinical modulation of the lymphatic reserve for tissue drainage has demonstrated promise and also generated conflicting results thus far. A better understanding of the hydraulic element of hypertension and the role of lymphatics in maintaining fluid balance can open new approaches to prevent and treat hypertension and its consequences, such as heart failure.

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Section: Lymphatics Of the Heart In Hypertensionmentioning

confidence: 59%

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

Rossitto,

Bertoldi,

Rutkowski

et al. 2024

Hypertension

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“…Interestingly, the overexpression of Sirtuin 3 stimulates the expression of Ang-1/Tie-2 while reducing the expression of ang2 [38,39]. Additionally, Sirtuin 3 overexpression induces the expression of HIF2α and Notch3 [38,39]. Based on the above experimental evidence, it suggests that the induction of HIF2α may limit inflammation and promote endothelial cell survival by preserving the barrier integrity (Figure 2).…”

Section: Hif2a Expression and Inflammationmentioning

confidence: 93%

“…Mechanistically, LPS stimulation suppresses the expression of Sirtuin-3, HIF2α, and Notch3 while promoting the expression of PHD2 and ang2 (Figure 2). Interestingly, the overexpression of Sirtuin 3 stimulates the expression of Ang-1/Tie-2 while reducing the expression of ang2 [38,39]. Additionally, Sirtuin 3 overexpression induces the expression of HIF2α and Notch3 [38,39].…”

Section: Hif2a Expression and Inflammationmentioning

confidence: 98%

Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy

Ullah

Humayun

et al. 2023

Biology

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Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases. Among the HIF isoforms, HIF2α is predominantly expressed in cardiac vascular endothelial cells and has a key role in cardiovascular diseases. HIFβ, also known as ARNT, is the obligate binding partner of HIFα subunits and is necessary for HIFα’s transcriptional activity. ARNT itself plays an essential role in the development of the cardiovascular system, regulating angiogenesis, limiting inflammatory cytokine production, and protecting against cardiomyopathy. This review provides an overview of the current understanding of HIF2α and ARNT signaling in endothelial cell function and dysfunction and their involvement in IHD pathogenesis. We highlight their roles in inflammation and maintaining the integrity of the endothelial barrier, as well as their potential as therapeutic targets for IHD.

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“…SIRT3 is a major mitochondrial deacetylase closely associated with angiogenesis. A recent study indicated that SIRT3 activation upregulates the VEGF-C-VEGFR3 signaling axis protein expression, thereby promoting migration and proliferation of lymphatic endothelial cells (LECs), and lymphangiogenesis in AngⅡ-induced hypertensive heart models ( 73 , 74 ). Details are provided in Table IV and Fig.…”

Section: Lymphangiogenesis and Cardiovascular Diseasementioning

confidence: 99%

Lymphangiogenesis: A new strategy for heart disease treatment (Review)

Bai,

Wang,

et al. 2024

Int J Mol Med

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Heart disease remains a global health challenge, contributing notably to morbidity and mortality. The lymphatic vasculature, an integral component of the cardiovascular system, plays a crucial role in regulating essential physiological processes, including fluid balance, transportation of extravasated proteins and immune cell trafficking, all of which are important for heart function. Through thorough scientometric analysis and extensive research, the present review identified lymphangiogenesis as a hotspot in cardiovascular disease research, and the mechanisms underlying impaired cardiac lymphangiogenesis and inadequate lymph drainage in various cardiovascular diseases are discussed. Furthermore, the way used to improve lymphangiogenesis to effectively regulate a variety of heart diseases and associated signaling pathways was investigated. Notably, the current review also highlights the impact of Traditional Chinese Medicine (TCM) on lymphangiogenesis, aiming to establish a clinical basis for the potential of TCM to improve cardiovascular diseases by promoting lymphangiogenesis.

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Sirtuin 3 deficiency aggravates angiotensin II‐induced hypertensive cardiac injury by the impairment of lymphangiogenesis

Cited by 9 publications

References 42 publications

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy

Lymphangiogenesis: A new strategy for heart disease treatment (Review)

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