Biomaterial Database

Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling. 2022

Yusuke Adachi, and Kazutaka Ueda, and Seitaro Nomura, and Kaoru Ito, and Manami Katoh, and Mikako Katagiri, and Shintaro Yamada, and Masaki Hashimoto, and Bowen Zhai, and Genri Numata, and Akira Otani, and Munetoshi Hinata, and Yuta Hiraike, and Hironori Waki, and Norifumi Takeda, and Hiroyuki Morita, and Tetsuo Ushiku, and Toshimasa Yamauchi, and Eiki Takimoto, and Issei Komuro

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulate in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbates inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuates inflammation and pathological vascular remodeling. Single-cell RNA sequencing reveals that beige adipocytes abundantly express neuregulin 4 (Nrg4) which critically regulate alternative macrophage activation. Importantly, significant beiging is observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induces the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitates alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrates the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D002001	Adipose Tissue, Brown	A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids.	Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D050197	Atherosclerosis	A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.	Atherogenesis,Atherogeneses,Atheroscleroses
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057772	Vascular System Injuries	Injuries to blood vessels caused by laceration, contusion, puncture, or crush and other types of injuries. Symptoms vary by site and mode of injuries and may include bleeding, bruising, swelling, pain, and numbness. It does not include injuries secondary to pathologic function or diseases such as ATHEROSCLEROSIS.	Vascular Injuries,Injuries, Vascular,Injuries, Vascular System,Injury, Vascular,Injury, Vascular System,System Injuries, Vascular,System Injury, Vascular,Vascular Injury,Vascular System Injury
D066253	Vascular Remodeling	The active alterations of vascular wall structures, often leading to elevated VASCULAR RESISTANCE. It is associated with AGING; ATHEROSCLEROSIS; DIABETES MELLITUS; HYPERTENSION; PREGNANCY; PULMONARY HYPERTENSION; and STROKE, but is also a normal part of EMBRYOGENESIS.	Pulmonary Arterial Remodeling,Arterial Remodeling, Pulmonary,Arterial Remodelings, Pulmonary,Pulmonary Arterial Remodelings,Remodeling, Pulmonary Arterial,Remodeling, Vascular,Remodelings, Pulmonary Arterial,Remodelings, Vascular,Vascular Remodelings