CN116036233A - Application of small molecular compound PMX53 in preparation of medicines for inhibiting vascular calcification and vascular fibrosis - Google Patents

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of a small molecular compound PMX53 in preparation of a medicament for inhibiting vascular calcification and vascular fibrosis. In order to overcome the problems that VC and VF cause higher incidence and mortality of cardiovascular diseases and lack of effective and low-cost clinical medicines, the invention discovers that PMX53 can obviously inhibit VSMCs from osteogenic transdifferentiation and COL1α1 expression, thereby delaying the progress of VC and VF. The mechanism of action of PMX53 in regulating VC and VF may be related to its inhibition of activation of the endoplasmic reticulum stress pathway PERK-eif2α -ATF4 and thus the inhibition of osteogenic transdifferentiation of VSMCs and expression of COL1 α1. Because PMX53 has remarkable effect of inhibiting VC and VF, better drug safety and pharmacokinetics, low cost, easy acquisition and flexible and various administration modes, the PMX53 is expected to be a candidate drug for resisting VC and VF.

Description

Application of small molecular compound PMX53 in preparation of medicines for inhibiting vascular calcification and vascular fibrosis

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to application of a small molecular compound PMX53 in preparation of a medicament for inhibiting vascular calcification and vascular fibrosis.

Background

Vascular Calcification (VC) is the central pathological basis leading to high morbidity and mortality in cardiovascular disease. VC is an abnormal deposit of calcium phosphate in the vessel wall, mainly in the form of hydroxyapatite. VC lesions can involve the intima and media of arteries, resulting in increased stiffness of the vessel wall, thereby inducing the onset of cardiovascular disease. Over the last several decades, researchers have conducted extensive research on VC, revealing that the mechanism of VC is not only a result of high phosphorus and calcium environments, but is also a multifactorial involved and subject to highly regulated active processes, including imbalance between cellular osteogenic transdifferentiation and anti-calcification signaling.

The pathology of Vascular Fibrosis (VF) is the deposition of collagen in the vessel wall, and is dominated by type I collagen. In VF, vascular Smooth Muscle Cells (VSMCs) transdifferentiate towards a synthetic phenotype, being the primary cell expressing type I collagen, with an accompanying increase in Osteopontin (OPN) expression. VF increases the stiffness of the vessel wall and reduces the elasticity of the vessel wall, thereby leading to the occurrence of various cardiovascular diseases. In addition to changes in VC, changes in VF were observed in the high adenine high phosphorus (AP) mouse model and the high phosphorus induced VSMCs in vitro cell model. Core lesions of VC are osteogenic transdifferentiation of VSMCs, manifested by increased expression of markers associated with the osteogenic phenotype (RUNX 2, BMP2, etc.) and decreased expression of markers associated with the contractile phenotype (SM 22 a, a-SMA, etc.); VF is primarily characterized by VSMCs transdifferentiated to a synthetic phenotype such that type I collagen and OPN expression is increased (Peng J, qin C, tian SY, peng JQ. MiR-93inhibits the vascular calcification of chronic renal failure by suppression of Wnt/beta-catenin pathway. Int. Urol Nephrol2022;54:225-235.; ren LS, zhang L, zhu D, li T, wang Q, yuan XY, hao LR. KMUP-1regulates the vascular calcification in chronic renal failure by mediating NO/cGMP/PKG signaling pathway. Life Sci 2020;253:117683.; ouyang L, su X, li W, tang L, zhang M, zhu Y, xie C, zhang P, chen J, huang H.ALK 1-demethylated DNAN-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney diseae. J Clin e 1; 131).

Persistent low system inflammation, extracellular matrix remodeling, oxidative stress, autophagy, DNA damage, the immune system, etc. may be involved in the progression of VC and VF. Although extensive research has explored various pathogenesis of VC and VF, providing a direction and target for slowing the progression of this emerging health problem, there is still a lack of clinically effective drugs for the treatment of VC and VF. VSMCs are the major participants in VC and VF, and VSMCs osteogenic transdifferentiation is a key link to VC, with synthetic phenotype VSMCs being the major source of type I collagen. Thus, inhibition of VSMCs osteogenic transdifferentiation and type I collagen expression is critical for slowing the progression of VC and VF. VSMCs osteogenic transdifferentiation exhibited increased expression of the osteogenic phenotype-associated markers (RUNX 2, BMP2, etc.) and decreased expression of the contractile phenotype-associated markers (SM 22. Alpha.,. Alpha. -SMA, etc.). The increase in type I collagen synthesis is mainly detected by western blot detection, masson staining, immunohistochemistry and the like to detect the change of the expression level of type I collagen alpha 1 (COL 1 alpha 1). The current research is mainly focused on how to regulate the expression of factors such as RUNX2, BMP2, COL1 alpha 1 and the like in VSMCs from the epigenetic level, but how to convert the factors into clinical drugs for treating VC and VF, which have a plurality of difficulties and challenges in the middle, and require more basic and preclinical research to further explore. Although there have been some studies to find that some natural compounds or some drugs (such as spermidine, gallic acid, metformin, etc.) can delay the progress of VC by inhibiting osteogenic transdifferentiation of VSMCs, mitoQ delays the progress of VF by inhibiting the expression of COL 1a 1. However, the absence of specific receptors for the above natural compounds or drugs on VSMCs results in an inability to guarantee effective drug utilization and specificity of targeted VSMCs. And the half-life of the natural compound is short, so that the effective drug concentration in the body can not be ensured.

In summary, the development of novel, efficient and inexpensive anti-VC and VF drugs is of great importance for reducing the high incidence and mortality of cardiovascular disease.

Disclosure of Invention

In order to overcome the problems that VC and VF cause higher morbidity and mortality of cardiovascular diseases and lack of effective and cheap clinical medicines, the invention provides a brand-new application of a small molecular compound PMX53, namely, the PMX 53-based compound PMX53 has better medicine safety and stronger inhibition effect on VC and VF, and the compound PMX 53-based compound PMX has the effect of being used as a candidate medicine for resisting VC and VF.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

the invention provides application of a small molecular compound PMX53 in preparing a medicament for inhibiting vascular calcification and/or vascular fibrosis.

Preferably, the vascular calcification and/or vascular fibrosis is vascular calcification and/or vascular fibrosis caused by high adenine hyperphosphorylation.

According to the invention, the small molecular compound PMX53 is found to be used as a specific antagonist of C5aR1, can be combined with C5a receptor C5aR1 on the surface of VSMCs in a high affinity competitive manner, further has a strong inhibition effect on VC and VF, can achieve effective drug concentration in vivo, has good drug safety, and is low in cost and easy to obtain.

Preferably, the inhibition of vascular calcification inhibits or reduces the osteogenic phenotype transdifferentiation of VSMCs.

Preferably, the inhibition of vascular fibrosis inhibits or reduces the expression of COL1 alpha 1.

According to the invention, the PMX53 can inhibit VSMCs osteogenic phenotype transdifferentiation and COL1α1 expression, so as to achieve the effect of delaying VC and VF.

Preferably, said inhibiting or reducing the osteogenic phenotype transdifferentiation of the VSMCs is effected by inhibiting activation of the PERK-eIF2 alpha-ATF 4 signaling pathway.

Preferably, said inhibiting or reducing the expression of COL1α1 is achieved by inhibiting the activation of the PERK-eIF2α -ATF4 signaling pathway.

Further research of the invention shows that PMX53 can inhibit osteogenic transdifferentiation of VSMCs and expression of COL1α1 by inhibiting activation of endoplasmic reticulum stress pathway PERK-eIF2α -ATF4, and finally delay progression of VC and VF.

The invention also provides a drug for inhibiting vascular calcification or a drug for inhibiting vascular fibrosis, which takes a small molecular compound PMX53 as a main active ingredient.

Preferably, pharmaceutically acceptable excipients are also included. The auxiliary materials are diluents, adhesives, lubricants, disintegrants, cosolvents, stabilizers and the like which can be used in the pharmaceutical field and some medicinal matrixes; the functional pharmaceutical excipients can also be obtained in the pharmaceutical field, and comprise surfactants, suspending agents, emulsifying agents and some novel pharmaceutical polymer materials, such as cyclodextrin, chitosan, polylactic acid (PLA), polyglycolic acid-polylactic acid copolymer (PLGA), hyaluronic acid and the like.

Preferably, the dosage forms of the medicine comprise injection, injection powder, tablet, granule, capsule, dripping pill, sustained release agent and oral liquid preparation. PMX53 is a known small molecule drug which can be dissolved in Phosphate Buffer Solution (PBS) or dimethyl sulfoxide, has good thermal stability, low cytotoxicity and good drug safety, has good pharmacokinetic properties, and can be flexibly administered by various modes such as oral administration, subcutaneous injection, intramuscular injection, intravenous injection and the like.

The above-mentioned dosage forms refer to clinically usual dosage forms, and the pharmaceutical preparation may be administered orally or parenterally (e.g. intravenously, subcutaneously, intraperitoneally or topically), and if some drugs are unstable under gastric conditions, may be formulated as enteric coated tablets.

Compared with the prior art, the invention has the beneficial effects that:

VC and VF are clinically common vascular pathological changes that lead to higher morbidity and mortality in cardiovascular disease. However, there is currently no effective, inexpensive clinical drug. Therefore, the invention provides a brand-new application direction of a small molecular compound PMX53, and the PMX53 can obviously inhibit the osteogenic transdifferentiation of VSMCs and the expression of COL1α1, thereby delaying the progress of VC and VF. Furthermore, the mechanism of action of PMX53 in regulating VC and VF is associated with its inhibition of activation of endoplasmic reticulum stress PERK-eif2α -ATF4 signaling pathway, which can be used to inhibit VSMCs osteogenic transdifferentiation and col1α1 expression, ultimately slowing the progression of VC and VF. Therefore, the PMX53 is expected to be a candidate drug for resisting VC and VF, provides high-efficiency and low-cost small molecular compounds for resisting VC and VF, and simultaneously provides a new thought and a new target point for treating VC and VF.

Drawings

FIG. 1 shows the up-regulation of C5aR1 expression during VC and VF [ A) Von Kossa staining of radial artery sections of VC and VF, immunohistochemical staining of COL1α1 and C5aR1, scale bar, 100 μm; (B) In vivo model aortic section Von Kossa staining, COL in control and AP miceImmunohistochemical staining of 1α1 and C5aR1, scale bar, 200 μm; (C-D) Western blot analysis (C) and quantification (D) of expression of C5aR1, COL1α1 and osteogenic transdifferentiation index (RUNX 2) in the aorta of the in vivo model of control and AP mice. Alizarin red staining and Western blot analysis results (E) of (E-G) VSMCs 7 days after exposure to Pi (0, 2.2, 2.4, 2.6, 2.8, 3.0 mM), and quantitative analysis results (F-G, F, G for sequentially 0, 2.2, 2.4, 2.6, 2.8, 3.0mM Pi from left to right) of col1α1, C5aR1, osteogenic transdifferentiation markers (BMP 2, RUNX 2) and contractile phenotype markers (SM 22 α, α -SMA) expression; (H) mRNA expression levels of C5aR1 in VSMCs exposed to Pi (2.6 mM) for 72 h; all values are expressed as mean ± SEM, ^* P<0.05】；

FIG. 2 shows PMX53 inhibition of VSMCs osteogenic phenotype transdifferentiation and COL1α1 expression [ first, after half an hour of pretreatment with 1.25,2.5 and 5.0. Mu.M PMX53, VSMCs were incubated for 7 days with 2.6mM Pi and 100ng/mL recombinant human complement C5a, and then analyzed by alizarin red staining and Western blot (A), and quantitative analysis (B-C, B, C, from left to right, for changes in expression of Control, pi, pi +100ng/mL C5a, pi+100ng/mL C5a+1.25. Mu.M PMX53, pi+100ng/mL C5a+2.5. Mu.M PMX53, pi+100ng/mL C5a+5. Mu.M PMX 53) COL1α1, osteogenic transdifferentiation markers (BMP 2, RUNX 2) and shrinkage phenotype markers (SM 22. Alpha.,. Alpha. -SMA), all expressed as mean.+ -. SEM, ^* P<0.05】；

fig. 3 shows PMX53 delays progression of VC and VF [ wild type mice were randomly divided into 4 groups of 15 animals each, control group fed with mouse maintenance diet without any addition, AP group fed with mouse maintenance diet with high adenine (0.15%) and phosphorus (1.5%); meanwhile, AP plus Phosphate Buffer Solution (PBS) group subcutaneous injection PBS (1 mL/Kg/day), AP plus PMX53 group subcutaneous injection PMX53 (1 mg/Kg/day), then calcium content (A) in aortic blood vessels was evaluated by alizarin red staining, type I collagen content (B) in aortic blood vessels was evaluated by Masson staining, western blot (C) and quantitative analysis (Control, AP, AP +PBS, AP+PMX53) were sequentially carried out from left to right in D) of expression changes of COL1α1, osteogenic transdifferentiation markers (BMP 2, RUNX 2) and contractile phenotype markers (SM 22. Alpha.,. Alpha. -SMA), all values were expressed as mean.+ -. SEM, ^* P<0.05】；

FIG. 4 shows PMX53 reduced the osteogenic phenotype transdifferentiation of VSMCs and the expression of COL1α1 by inhibition of PERK-eIF2α -ATF4 signaling pathway [ through Western blot and quantitative analysis of changes in expression of endoplasmic reticulum stress-related markers (glucose regulatory protein 94 (GRP 94), glucose regulatory protein 78 (BIP) and endoplasmic reticulum stress primary sensors (PERK, IRE1α, ATF 6) in mouse in vivo model aorta (A-B, in left to right in order Control, AP, AP +PBS, AP+PMX53) and in vitro cell model VSMCs (C-E, D, E, in left to right in Control, pi, pi +C5a, pi+C5a+PMX53), all expressed as mean.+ -. SEM, ^* P<0.05】。

Detailed Description

The following describes the invention in more detail. The description of these embodiments is provided to assist understanding of the present invention, but is not intended to limit the present invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.

The experimental methods in the following examples, unless otherwise specified, are conventional, and the experimental materials used in the following examples, unless otherwise specified, are commercially available.

EXAMPLE 1 anti-vascular calcification and vascular fibrosis study of the Small molecule Compound PMX53

1. Materials and methods

1.1, experimental materials

Primary human vascular smooth muscle cells were purchased from american type culture collection library; c57BL/6J male wild mice (weight 20-25 g) at 8 weeks old were purchased from university laboratory animal center in Zhongshan, and both the mouse maintenance feed and the high adenine and high phosphorus added mouse maintenance feed were purchased from the Wuhan Yutaihe science and technology Co., ltd; PMX53 (molecular formula C) ₄₇ H ₆₅ N ₁₁ O ₇ ) Purchased from RD; inorganic phosphorus was purchased from Sigma; recombinant human complement C5a was purchased from RD.

1.2, experimental method:

1.2.1 cell culture and in vitro cell model

Primary human aortic smooth muscle cells were cultured in DMEM medium containing 10% fetal bovine serum, 100U/mL penicillin, 100 μg/mL streptomycin at 37 ℃ in a 5% carbon dioxide cell incubator. To induce in vitro calcification and fibrosis models, counts were about 1×10 ⁶ VSMCs plates were plated in six well plates for 24 hours before medium was changed and inorganic phosphorus (Pi) was added, pi final concentration was 2.6mM, incubated for 7 days, medium and Pi were changed every 2 days.

1.2.2 in vivo mouse model and tissue acquisition

In the in vivo model of the high adenine high phosphorus (AP) mouse, two lesions of VC and VF are confirmed to exist, so that the embodiment carries out subsequent experiments through the same modeling, namely, the in vivo model of the mouse is constructed by feeding high adenine high phosphorus diet, and the influence of PMX53 on the two diseases of VC and VF is detected. Wild type mice were randomly divided into 4 groups of 15 animals each, with the control group fed with mouse maintenance feed without any addition and the AP group fed with high adenine (0.15%) high phosphorus (1.5%) mouse maintenance feed. Meanwhile, the AP-plus-PBS group was subcutaneously injected with PBS (1 mL/Kg/day) while feeding, and the AP-plus-PMX 53 group was subcutaneously injected with PMX53 (1 mg/Kg/day) while feeding. After 12 weeks of feeding and subcutaneous injection molding, aortic tissue was obtained after euthanasia of the mice.

1.2.3 effects of PMX53 on VCMCs osteogenic transdifferentiation and COL1α1 expression

Primary human aortic smooth muscle cells were grown at 1X 10 ⁶ The density of each well was inoculated into 6-well plates, 2mL of DMEM complete medium was added to each well, and after 24 hours, 1.25,2.5 and 5.0. Mu.M PMX53 were pre-treated for half an hour, respectively, followed by 2mL of complete medium, pi (final concentration 2.6 mM) and 100ng/mL of recombinant human complement C5a. PMX53, medium, pi, recombinant human complement C5a were changed every 2 days. After 7 days, the total cell proteins were extracted with RIPA for Western Blot analysis or calcium content assessment of cells by alizarin red staining.

2. Experimental results

2.1 up-regulation of C5aR1 expression during VC and VF

C5aR1 is expressed in VSMCs, macrophages, endothelial cells, etc., in order to observe the expression changes of C5aR1 (receptor 1 for complement protein C5 a) during VC and VF, calcium content in human radial artery and mouse aorta is assessed by Von Kossa staining, expression of COL1 α1 and C5aR1 in human radial artery and mouse aorta is detected by immunohistochemical method, calcium content in VSMCs is assessed by alizing red staining, expression of C5aR1 in mouse model aorta and in vitro model VSMCs is detected by Western Blot method, and expression changes of C5aR1 mRNA in vitro model VSMCs are detected by RT-PCR method.

As a result, VC and VF radial arteries were found to exhibit higher C5aR1 expression than VC and VF free radial arteries (fig. 1A). Consistent with clinical observations of human radial arteries, C5aR1 levels in the mouse VC and VF aorta were higher than control, and COL1 α1 expression was significantly increased in the mouse VF aortic blood vessels (fig. 1B-D). In addition, in vitro models of VSMCs were constructed, alizarin red staining demonstrated that Pi dose-dependently induced calcium deposition in VSMCs. In Western Blot analysis, pi dose-dependent promotion of osteogenic transdifferentiation of VSMCs was observed, which was manifested by increased expression of the osteogenic phenotypic markers (BMP 2, RUNX 2) and decreased expression of the contractile phenotypic markers (SM 22 a, a-SMA), as well as Pi dose-dependent promotion of increased expression of COL 1a 1. Furthermore, at a Pi concentration of 2.6mM, it is statistically significant that the subsequent experiments were modeled using 2.6 mM. More importantly, the Pi dose dependence increased the protein expression level of C5aR1 during osteogenic transdifferentiation of VSMCs (fig. 1E-G). And the C5aR1 mRNA levels in the in vitro cell model VSMCs were significantly higher than in the control group (fig. 1H). These data indicate that C5aR1 is up-regulated during VC and VF in vivo and in vitro.

2.2 PMX53 inhibits VSMCs osteogenic phenotype transdifferentiation and COL1α1 expression

To explore the effect of PMX53 on VSMCs osteogenic phenotype transdifferentiation and COL1 α1 expression, expression levels of osteogenic transdifferentiation-related markers (RUNX 2, BMP 2) and contractile phenotype-related markers (SM 22 α, α -SMA), COL1 α1 were detected by Western Blot experiments following half hour pretreatment with 1.25,2.5 and 5.0 μm PMX53 in an in vitro cell model followed by calcium content assessment by alizing with alizarin red staining with 2.6mM Pi and 100ng/mL recombinant human complement C5a.

Alizarin staining suggests that PMX53 dose-dependently reduces calcium deposition in VSMCs. Western blot analysis showed that 5.0. Mu.M PMX53 significantly inhibited the increase in bone transdifferentiation markers (RUNX 2, BMP 2) expression, whereas the expression of contraction markers (SM 22. Alpha.,. Alpha. -SMA) was reversed and the expression level of COL1α1 was significantly reduced. PMX53 was shown to inhibit VSMCs osteogenic transdifferentiation and COL1α1 expression (FIGS. 2A-C).

2.3, PMX53 defer VC and VF Process

To further explore the effect of PMX53 on VC and VF, mice aortic was obtained after modeling by constructing an in vivo model and subcutaneously injecting PMX53 or PBS, calcium content in aortic vessels was assessed by alizarin staining, type I collagen content in aortic vessels was assessed by Masson staining, western blot detected for the relevant markers of osteogenic and contractile phenotypes in aortic vessels and changes in COL1 α1 expression levels.

The alizarin staining of the whole root vessels suggested a significant decrease in calcium deposition in aortic vessels in the ap+pmx53 group compared to the ap+pbs group (fig. 3A). Masson staining suggested that the type I collagen content in aortic vessels was significantly reduced in the ap+pmx53 group compared to the ap+pbs group. Western blot analysis showed that PMX53 reduced expression of RUNX2, BMP2 and COL 1a 1 in calcified mouse aorta, whereas expression of contraction markers (SM 22 a, a-SMA) was increased compared to ap+pbs group (fig. 3B-C). The data indicates that PMX53 can delay the progression of VC and VF.

2.4 PMX53 reduces VSMCs osteogenic phenotype transdifferentiation and COL1α1 expression by inhibiting activation of PERK-eIF2 α -ATF4 signaling pathway

Since VC and VF are highly regulated by endoplasmic reticulum stress (endoplasmic reticulum stress pathways total 3: PERK-eIF2α -ATF4, IRE1 α -XBP1 and ATF 6). For this reason, it was next investigated whether PMX53 delays VC and VF by modulating endoplasmic reticulum stress. The changes in the expression of endoplasmic reticulum stress related markers (glucose regulatory protein 94 (GRP 94) and glucose regulatory protein 78 (GRP 94)) and endoplasmic reticulum stress primary sensors (PERK, IRE 1a, ATF 6) in mouse in vivo model aorta and in vitro model VSMCs were detected by Western blot.

The results suggest that VC and VF processes induce activation of endoplasmic reticulum stress, manifested as increased levels of endoplasmic reticulum stress markers (GRP 94 and BIP) in vivo and in vitro (fig. 4A-E). Interestingly, C5a-C5aR1 significantly increased the levels of pPERK, but not pIRE1α and ATF6, and increased the levels of factors peIF-2α and ATF4 downstream of the PERK signaling pathway. Meanwhile, after PMX53 pretreatment, the expression of GRP94 and BIP is obviously reduced, which suggests that PMX53 inhibits the stress activation of the endoplasmic reticulum. And PMX53 further inhibited activation of endoplasmic reticulum stress PERK-eif2α -ATF4 signaling pathway (fig. 4A-E). It was shown that PMX53 can reduce VSMCs osteogenic phenotype transdifferentiation and COL1α1 expression by inhibiting activation of PERK-eIF2α -ATF4 signaling pathway.

Taken together, it can be seen that the small molecule compound PMX53, which is a specific antagonist of C5aR1, is capable of competitively binding to C5aR1 on the surface of VSMCs with high affinity, and then inhibiting osteogenic transdifferentiation of the VSMCs and expression of COL1α1 by inhibiting activation of the endoplasmic reticulum stress pathway PERK-eIF2α -ATF4, and finally delaying progression of VC and VF, and is expected to be a candidate drug against VC and VF.

The embodiments of the present invention have been described in detail above, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, and yet fall within the scope of the invention.

Claims (9)

1. Use of a small molecule compound PMX53 for the preparation of a medicament for inhibiting vascular calcification and/or vascular fibrosis.

2. Use according to claim 1, characterized in that vascular calcification and/or vascular fibrosis is caused by high adenine hyperphosphorylation.

3. The use according to claim 1, wherein the inhibition of vascular calcification is inhibition or reduction of vascular smooth muscle cell osteogenic phenotype transdifferentiation.

4. The use according to claim 1, wherein said inhibition of vascular fibrosis inhibits or reduces the expression of type I collagen α1.

5. The use according to claim 3, wherein said inhibiting or reducing vascular smooth muscle cell osteoblastic phenotype transdifferentiation is achieved by inhibiting activation of the PERK-eif2α -ATF4 signaling pathway.

6. The use according to claim 4, wherein said inhibition or reduction of the expression of type I collagen α1 is achieved by inhibiting the activation of the PERK-eif2α -ATF4 signaling pathway.

7. A medicament for inhibiting vascular calcification or a medicament for inhibiting vascular fibrosis, which is characterized in that the medicament takes a small molecular compound PMX53 as a main active ingredient.

8. The agent for inhibiting vascular calcification or inhibiting vascular fibrosis of claim 7, further comprising a pharmaceutically acceptable excipient.

9. The drug for inhibiting vascular calcification or drug for inhibiting vascular fibrosis according to claim 7, wherein the dosage forms of the drug include injection, injection powder, tablet, granule, capsule, dripping pill, sustained release preparation and oral liquid preparation.

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