CN-122012694-A - Application of ACSS2 as target in screening or preparing medicine for treating virus-induced vascular remodeling

Abstract

The invention discloses an application of ACSS2 as an action target in screening or preparing a medicament for preventing or treating virus-induced vascular superplastic diseases, and belongs to the field of biological medicines. The invention discovers that the vascular smooth muscle cell phenotype transformation induced by the transcription-kavirus can be obviously reversed by inhibiting ACSS2 gene expression or protein activity, and the occurrence and development of aortic aneurysm/interlayer induced by angiotensin II/aminopropionitrile can be reduced. The invention provides a siRNA sequence (SEQ ID NO. 1-2) of specific targeting ACSS2 and a pharmaceutical composition containing the siRNA, and provides a novel therapeutic target and an accurate intervention tool for virus-related vascular superplastic diseases.

Inventors

• ZHENG CHANGBO
• Gao Wencong
• CHEN PENG
• MA XIN
• ZHOU XIAOHUAN
• TAN JIAXIANG
• Wang Binbao

Assignees

• 昆明医科大学

Dates

Publication Date

20260512

Application Date

20260210

Claims (10)

1. 1. The application of ACSS2 as an action target in screening or preparing medicaments for preventing or treating virus-induced vascular superplastic diseases.
2. 2. Use of an ACSS2 inhibitor in the manufacture of a medicament for the prevention and/or treatment of virus-induced vascular superplastic disease.
3. 3. The use according to claim 2, wherein the virus is a zika virus or dengue virus and the vascular remodeling disorder is intimal hyperplasia, aortic aneurysm, aortic dissection, atherosclerosis, restenosis.
4. 4. The use according to claim 3, wherein the ACSS2 inhibitor is a nucleic acid inhibitor, a small molecule compound or an antibody capable of inhibiting the expression of an ACSS2 gene or the activity of a protein.
5. 5. The use according to claim 4, wherein the nucleic acid inhibitor is an siRNA.
6. 6. The use according to any one of claims 2 to 5, wherein the medicament reduces ACSS2 expression in vascular smooth muscle cells, restores the expression levels of α -smooth muscle actin and smooth muscle 22 α, inhibits abnormal upregulation of osteopontin.
7. 7. Use of an siRNA that specifically inhibits ACSS2 for the manufacture of a medicament comprising a first strand as shown in SEQ ID No.1 and a second strand as shown in SEQ ID No. 2 for the prevention or treatment of vascular superplastic diseases induced by viral infections.
8. 8. The use according to claim 7, wherein said medicament is for preventing or treating vascular smooth muscle cell phenotype transformation induced by zika virus infection.
9. 9. The use according to claim 8, wherein the medicament is for preventing or treating aortic aneurysm or aortic dissection initiated or exacerbated by the vascular smooth muscle cell phenotype transformation.
10. 10. A pharmaceutical composition comprising an effective amount of the double stranded nucleic acid molecule of claim 9 and a pharmaceutically acceptable carrier.

Description

Application of ACSS2 as target in screening or preparing medicine for treating virus-induced vascular remodeling Technical Field The invention relates to the field of biological medicine, in particular to application of ACSS2 serving as an action target in screening or preparing a medicament for preventing or treating virus-induced vascular superplastic diseases, and related inhibitors, nucleic acid molecules and pharmaceutical compositions. Background Vascular remodeling (Vascular Remodeling) is a common pathological basis for a variety of vascular diseases, and is essentially the adaptive regulation of structure and function of the vessel wall to cope with changes in internal and external environments, particularly in the dynamic changes of wall thickness, lumen diameter and vessel function. Vascular smooth muscle cells (Vascular Smooth Muscle Cells, VSMCs) act as the major cellular component of the arterial vessel wall, exhibiting a contractile phenotype in physiological states, critical to maintaining normal vascular structure and function. However, under pathological conditions, the conversion of vascular smooth muscle cells from a contractile to a synthetic aberrant phenotype has become a central pathological feature of vascular remodeling. The imbalance in phenotype switching is involved in the occurrence and progression of various cardiovascular diseases, such as aortic aneurysms, aortic dissection, etc. Thus, intervention in the phenotypic switching of vascular smooth muscle cells is considered as a potential strategy to inhibit vascular remodeling. In recent years, research has found that certain virus infections, such as Zikv, not only cause lesions of the nervous system, but also possibly attack the vascular system and participate in inducing vascular remodeling, but the specific mechanism is unknown, and a targeted intervention strategy is also lacking. Therefore, the key molecular target of virus induced vascular remodeling is searched, and corresponding therapeutic drugs are developed, so that the method has important clinical significance and urgency. ACSS2 (acetyl-coa synthetase short chain family member 2) is a key enzyme that catalyzes the conversion of acetic acid to acetyl-coa, involved in cellular metabolism and epigenetic regulation. In the prior art, ACSS2 has been reported to be associated with tumors, metabolic diseases and the like, and studies have suggested that it may be associated with certain cardiovascular pathological processes. However, no technology has been disclosed to show that ACSS2 plays a key role in vascular remodeling induced by viral (especially zika virus) infection, and has not been proposed as a therapeutic target for this specific disease, and no effective therapeutic means for this target has been developed. Disclosure of Invention Aiming at the technical problems that the prior art lacks specific therapeutic targets and effective medicaments for vascular superplastic diseases induced by viruses (especially Zika viruses). The invention provides application of ACSS2 as an action target in screening or preparing medicaments for preventing or treating virus-induced vascular superplastic diseases, and related inhibitors, nucleic acid molecules and pharmaceutical compositions. The invention is realized by the following technical scheme: In a first aspect, the invention provides the use of ACSS2 as an action target in the screening or manufacture of a medicament for the prevention or treatment of virus-induced vascular superplastic disease. Preferably, the use is the use of a method of screening for candidate substances capable of modulating ACSS2 expression or activity. The method comprises providing a vascular smooth muscle cell model of viral infection expressing ACSS2, adding candidate substances to the model, and detecting a change in a phenotypic marker of vascular smooth muscle cells, wherein candidate substances capable of reversing virus-induced synthetic phenotypic conversion are screened as potential drugs. In a second aspect, based on the above targets, the invention provides application of an ACSS2 inhibitor in preparing a medicament for preventing and/or treating virus-induced vascular remodeling diseases. Preferably, the virus is a Zika virus or dengue virus. Such vascular superplastic diseases include, but are not limited to, intimal hyperplasia, aortic aneurysm, aortic dissection, atherosclerosis, restenosis. The ACSS2 inhibitor is a substance capable of inhibiting ACSS2 gene expression or protein activity, such as a nucleic acid inhibitor, a small molecule compound or an antibody. Preferably, the nucleic acid inhibitor is an siRNA (small interfering RNA). In a third aspect, the invention provides in particular the use of an siRNA that specifically inhibits ACSS2 in the manufacture of a medicament. The siRNA comprises a first strand as shown in SEQ ID NO. 1 and a second strand as shown in SEQ ID NO. 2. The medicine is used for preventing or treati