Medicine for treating coronary artery calcification

Abstract

The invention relates to the technical field of biological medicine, in particular to application of pterostilbene serving as an Orai1 protein inhibitor to preparation of a medicine for treating coronary artery calcification. By using the Orai1 protein inhibitor pterostilbene, accurate treatment of coronary artery calcification can be realized, the occurrence proportion of serious coronary artery calcification is reduced, and economic and social burdens brought by surgical treatment are reduced.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and more particularly to the use of pterostilbene in preparing a drug for treating coronary artery calcification. Background Art

[0002] Coronary artery calcification refers to the process of calcium salt deposition within the coronary artery walls, leading to hardening and narrowing of the vessels. This can ultimately lead to coronary artery stenosis and insufficient blood flow, and can cause serious clinical consequences such as angina pectoris and acute myocardial infarction. Epidemiological studies have shown that the incidence of coronary artery calcification increases with age, reaching a peak of approximately 80% in people aged 60 to 80. The incidence is higher in men than in women in the same age group.

[0003] Currently, the primary treatment for coronary artery calcification is cardiovascular intervention. Percutaneous coronary intervention (PCI) is routinely used for mild to moderate calcified lesions, while rotational atherectomy (RAA) is used for moderate to severe calcified lesions and lesions that are impassable by the balloon.

[0004] Clinical drug treatments for coronary artery calcification primarily include drugs that can alleviate the progression of coronary atherosclerosis, such as simvastatin tablets, atorvastatin calcium tablets, and ezetimibe tablets, and drugs that can inhibit platelet aggregation, such as enteric-coated aspirin tablets and clopidogrel bisulfate tablets. However, these drugs target the causes of coronary artery calcification, not the underlying mechanisms of its development. There is an urgent clinical need for a precise therapeutic approach targeting these targets. Therefore, exploring new prevention and treatment strategies is of great clinical significance for the control of vascular calcification. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a drug for treating coronary artery calcification.

[0006] The present invention provides the use of pterostilbene in preparing a medicine for treating coronary artery calcification.

[0007] Preferably, the pterostilbene is used as the sole active ingredient in the preparation of the medicine.

[0008] Preferably, the pterostilbene is used together with other active ingredients in the preparation of the medicine.

[0009] Preferably, the drug is selected from one or more of oral preparations or injections.

[0010] Preferably, the oral preparation is one or more of capsules, tablets, oral liquids, granules, pills, powders, pills or pastes.

[0011] Preferably, the injection is administered by one or more of subcutaneous administration, intramuscular administration or intravenous administration.

[0012] Preferably, the drug also contains one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers include, for example, various organic or inorganic carrier substances commonly used as formulation materials, which can be used as excipients, lubricants, binders, disintegrants, and thickeners in solid formulations; and as solvents, dispersants, solubilizers, suspending agents, tonicity agents, buffers, analgesics, and the like in liquid formulations, and are formulated in appropriate amounts. Additionally, additives such as preservatives, antioxidants, colorants, and sweeteners can be used as needed according to conventional methods.

[0013] Preferred examples of excipients include lactose, sugar, D-mannitol, starch, crystalline cellulose, and light anhydrous silicic acid. Preferred examples of lubricants include magnesium stearate, calcium stearate, talc, and colloidal silicon dioxide. Preferred examples of binders include crystalline cellulose, sugar, D-mannitol, dextrin, hydroxypropyl cellulose, and polyvinyl pyrrolidone. Preferred examples of disintegrants include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, and sodium carboxymethyl starch. Preferred examples of thickeners include natural gums, cellulose derivatives, and acrylic acid polymers. Preferred examples of solvents include water for injection, alcohol, propylene glycol, polyethylene glycol, sesame oil, and corn oil. Preferred examples of dispersants include Tween 80, HCO 60, polyethylene glycol, carboxymethyl cellulose, and sodium alginate. Preferred examples of solubilizers include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate. Preferred examples of suspending agents include stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate. Preferred examples of surfactants include polyvinyl alcohol, polyvinyl pyrrolidone, hydrophilic polymers such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose. Preferred examples of tonicity agents include sodium chloride, glycerol, and D-mannitol. Preferred examples of buffers include phosphates, acetates, carbonates, and citrates. Preferred examples of analgesics include benzyl alcohol. Preferred examples of preservatives include parabens, chlorobutanol, benzyl alcohol, phenylethyl alcohol, dehydroacetic acid, and sorbic acid. Preferred examples of the antioxidant include sulfites and ascorbic acid.

[0014] According to another aspect of the present invention, a method for inhibiting phosphate-induced coronary smooth muscle cell calcification in vitro is provided, wherein the coronary smooth muscle cells are treated with pterostilbene.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention can achieve precise treatment of coronary artery calcification through the Orai1 protein inhibitor pterostilbene, reduce the incidence of severe coronary artery calcification, and alleviate the economic and social burden of surgical treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of this application. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0018] Figure 1 3. This is a graph showing the inhibitory effect of different concentrations of pterostilbene on Orai1 channel-mediated calcium influx in coronary smooth muscle cells according to an embodiment of the present invention; Figure 1 A is a representative intracellular calcium concentration curve; Figure 1 B shows the relative increase in intracellular calcium concentration. F1 / F0 represents the ratio of the change in intracellular calcium concentration after extracellular calcium addition. P****<0.0001 compared with the DMSO solvent control.

[0019] Figure 2 This is a diagram showing the inhibitory effect of pterostilbene on phosphate-induced coronary smooth muscle cell calcification according to an embodiment of the present invention; Figure 2 A is a representative Alizarin red staining photograph at different time points; Figure 2 B is the statistical results of Alizarin Red staining of cells at different time points. Compared with CM, P****<0.0001

[0020] Figure 3 This is a diagram showing the inhibitory effect of pterostilbene on the expression of coronary smooth muscle cell calcification marker proteins OPN and RUNX2 according to an embodiment of the present invention; Figure 3 A is a representative immunoblot result; Figure 3 B and Figure 3 Densitometric statistics of COPN and RUNX2 proteins in immunoblotting results. Compared with CM, P**<0.01, P***<0.001.

[0021] Figure 4 Graph showing the effects of intraperitoneal injection of various drugs on calcification of the heart and coronary artery tissue in calcified rats according to an embodiment of the present invention. Figure 4 A is the myocardial photograph of each group; Figure 4 B is the results of Alizarin red staining of the coronary arteries in each group. Control: control group; VC: calcification group; VC+Synta66, VC+Nifedipine, and VC+Pterostilbene are VC combined with intraperitoneal injection of Synta66 (Orai1 inhibitor), Nifedipine, or Pterostilbene, respectively.

[0022] Figure 5 3 is a graph showing the effects of intraperitoneal injection of various drugs according to the embodiments of the present invention on the myocardial infarction area in rats with calcification and myocardial infarction. Figure 5 A is a representative TTC staining image of myocardial tissue; Figure 5 B is the statistical result of myocardial infarct area. VC: calcification alone group; VC + Synta66, VC + Nifedipine, and VC + Pterostilbene: VC combined with myocardial infarction and intraperitoneal injection of Synta66 (Orai1 inhibitor), Nifedipine, or Pterostilbene, respectively. ns: P > 0.05, P *** < 0.001, P **** < 0.0001. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings. It should be noted that the following examples do not limit the scope of protection claimed in the present invention and are merely illustrative examples. The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial sources.

[0024] Current treatments for coronary artery calcification

[0025] Drug Therapy: Vascular calcification is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) by producing proinflammatory cytokines such as interleukin-6 (IL-6), recombinant human interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and oncostatin M (OSM) in the intima and medial layers of the arterial wall. This process may be primarily mediated through the NF-κB signaling pathway. Vitamin K has been shown to exert anti-inflammatory effects by antagonizing NF-κB signaling, suggesting that vitamin K may prevent vascular calcification through anti-inflammatory mechanisms. Matrix Gla protein (MGP) inhibits soft tissue calcification and helps prevent intimal calcification. Vitamin K enhances MGP activity by promoting γ-carboxylation, thereby slowing the progression of vascular calcification. Other studies have shown that endothelial-to-mesenchymal transition (EndoMT) drives the endothelium to promote vascular calcification in diabetes, and glycogen synthase kinase-3β (GSK-3β) inhibition induces β-catenin, directing osteoblast-like cells to the endothelial lineage, thereby reducing vascular calcification in MGP deficiency.

[0026] Interventional Therapy: Traditional percutaneous coronary intervention (PCI) is the most common clinical approach for treating calcified lesions. However, advances in intravascular imaging technologies, such as IVUS and OCT, are revolutionizing the treatment of CAC. Current surgical procedures for treating calcified lesions can be categorized into two types: ablation and balloon-based techniques. The former, including rotational atherectomy (RA), orbital atherectomy (OA), and excimer laser, aim to ablate calcifications and facilitate stent expansion. The latter, including cutting balloons, ultrahigh-pressure balloons, and lithotripsy balloons, do not eliminate calcifications but instead aim to increase plaque elasticity or fragment calcified areas to allow stent expansion. Information obtained from intravascular imaging will enable the operator to select the most appropriate technique for treating calcified lesions. When the degree of calcification is moderate, the operator can use balloon-based techniques for lesion preparation, with lithotripsy balloons increasingly being used. Conversely, higher levels of calcification may still require more aggressive lesion preparation using ablative techniques such as RA or OA.

[0027] Example 1: Culture of primary coronary smooth muscle cells and induction of calcification

[0028] Prepare sterile surgical instruments in advance. Place the sterilized surgical instruments, culture dishes, and centrifuge tubes in a biosafety cabinet and irradiate with UV light for 20 minutes. Sacrifice a 200g male Sprague-Dawley rat with CO2. Spray the rat's chest and abdomen with alcohol, then carefully open the abdomen. Remove the heart and soak it in PBS. Wash it three times before placing it under a stereomicroscope to fix the heart. Isolate the coronary arteries under the microscope. Use sterile ophthalmic scissors and forceps to carefully dissect the myocardial tissue surrounding the coronary artery. Once the myocardial tissue is completely dissected, remove the coronary artery and wash it three times in PBS. Spray it with alcohol, then transfer it to a clean bench and wash it three more times with PBS. Place the coronary artery in complete culture medium and mince it with sterile ophthalmic scissors. Place it in a 6-well plate. Discard the medium and allow the tissue pieces to adhere. After 1 hour, add complete culture medium. Incubate at 37°C, 5% CO2. Observe adherence after 3 days. Change the medium every two days thereafter. After 10 days, subculture the cells into flasks for culture.

[0029] Calcification solution (CM): Accurately weigh a certain amount of Na2HPO4 and NaH2PO4 into DMEM medium at a ratio of 1:1 to a final concentration of 3 mM. Filter-sterilize the solution, add 2% FBS and 1% P / S, mix thoroughly by pipetting, tighten the cap, seal the bottle, and store at 4°C until needed.

[0030] Calcification Induction: Cells were seeded into 12-well plates and a calcification model was established when the cell density reached 70%. The complete culture medium was discarded and the cells were washed once with sterile PBS. 2% DMEM medium was added to the control group, while 2% calcification medium was added to the experimental group. The cells were cultured in a 37°C, 5% CO2 incubator, with the medium changed every two days. Cell morphology was observed daily. Subsequent experiments, including protein extraction, Alizarin Red S staining, and calcium content determination, were performed after 5, 7, and 10 days of calcification.

[0031] Example 2 Intracellular calcium determination

[0032] The cells were seeded into a 12-well plate containing a glass slide and subsequent experiments were performed when the cell density reached 60%-70%. Flou-8 was added to 500 μl of culture medium to make the concentration of Flou-8 10 μM and incubated for 30 min. The glass slide was removed and placed in OPSS (NaCl 4.099 g, KCl 0.18625 g, MgCl2 0.0475 g, C6H 12 O6 0.991g, HEPES 0.59575g were added to 500ml ddH2O and the pH was adjusted to 7.4) and rinsed twice. The cells were then placed in a bath and 450μl of OPSS was added for intracellular calcium fluorescence measurement. After stabilization, 2μM thapsigargin was added to release intracellular calcium. After stabilization, 2mM CaCl2 was added to allow calcium ions to enter the cells. The experiment was stopped after stabilization, and the ratio of F1 (fluorescence value after addition of agonist) / F0 (basal fluorescence value before agonism) was calculated as the rate of change of intracellular calcium concentration.

[0033] Example 3 Alizarin red staining of cells

[0034] Before staining, cells were fixed with 4% paraformaldehyde for 20 minutes; the fixative was extracted and 1 mL of Alizarin Red was added for staining at room temperature for 30 minutes; the stain was extracted and washed three times with acidic PBS to remove floating color; the cells were placed under a stereomicroscope and photographed; after the photograph was completed, 10% acetic acid solution was added to the wells, and the supernatant was aspirated and the absorbance value was measured at 405 nm for relative quantitative analysis of changes in calcium salt deposition.

[0035] Example 4 Protein immunoblotting experiment

[0036] Remove the cell culture medium from the cells and add 4°C pre-chilled PBS to the well plate. Wash twice, then add RIPA lysis buffer. Transfer all lysed proteins to a 1.5ml EP tube. After centrifugation, heat the well plate at 105°C for 15 minutes. Mix the protein with loading buffer and load it into an 8% SDS-PAGE gel lane. Add a marker to one well. Electrophoresis is performed at 70V to the stacking and separating gels. Continue at 120V until the desired proteins are completely separated. Discontinue electrophoresis. Prepare a PVDF membrane based on gel size. Place it in methanol for 10 seconds, then install it in a sandwich configuration in a transfer chamber. Fill the chamber with Transfer Buffer and run at 260mA for 90 minutes. After transfer, remove the PVDF membrane, add 5% skim milk, and block for 1.5 hours. After completion, the PVDF membrane was rinsed in PBST, placed in the corresponding antibody, and shaken at 4°C overnight; after washing on the next day, the PVDF membrane was placed in a box with secondary antibodies, shaken slowly at room temperature for 1.5 hours, and washed again with PBST three times for 10 minutes, exposed to ECL, and quantitatively analyzed using Image J software.

[0037] Example 5 Construction of an Animal Model of Coronary Artery Calcification

[0038] Clean-grade male Sprague-Dawley (SD) rats, 8 weeks old, weighing approximately 220 g, were fed a standard diet and purified water, with regular changes of feed, drinking water, and bedding. Animals were randomly assigned to each group during the experiment. Forty 8-week-old male SD rats were randomly divided into four groups: a calcification group (VC group), a control group (CON group), and a calcification + Synta66 group (VC+Synta66 group). The VC group received a single intramuscular injection of vitamin D3 dissolved in anhydrous ethanol (300,000 units / kg) and a single oral gavage of nicotine dissolved in peanut oil (25 mg / kg) on ​​day 1. The CON group received an intramuscular injection of anhydrous ethanol and a single oral gavage of peanut oil on the same day. The VC + Synta66 group was given Synta66 (30 mg / kg) on ​​top of the calcification model; the VC + Nifedipine group was given Nifedipine (0.2 mg / kg) on ​​top of the calcification model; and the VC + Pterostilbene group was given Pterostilbene (1 mg / kg) on ​​top of the calcification model. All three drugs were administered intraperitoneally every other day for 21 days (7 injections). All rats were fed a regular diet and purified water, with feed, drinking water, and bedding changed regularly.

[0039] Example 6 Construction of an animal model of acute myocardial ischemia

[0040] The rats were divided into coronary artery calcification group (VC), calcification ischemia group (VC+MI), calcification ischemia + Synta66 group (VC+MI+Synta66), calcification ischemia + Nifedipine group (VC+MI+Nifedipine), and calcification ischemia + pterostilbene group (VC+MI+Pterostilbene); among them, VC+MI+Synta66 group: Synta66 (10 mg / kg) was given on the basis of the calcification ischemia model; VC+MI+Nifedipine group: Nifedipine (0.2 mg / kg) was given on the basis of the calcification ischemia model; VC+MI+Pterostilbene group: Pterostilbene (1 mg / kg) was given on the basis of the calcification ischemia model. The above three drugs were all injected intraperitoneally, once every other day, for 21 days (7 times). All rats were fed with conventional feed and purified water, and the feed, drinking water and bedding were changed regularly. After the coronary calcification model was established, each group was intraperitoneally injected with 80 mg / kg isoproterenol hydrochloride. 24 hours later, each group was intraperitoneally injected with the same dose of isoproterenol hydrochloride again. After the model was established, blood, blood vessels and heart tissue were collected from the abdominal vein, and subsequent experiments were carried out (the myocardial ischemia in the present invention is based on the VC model, that is, VC causes stiffness of the coronary vessels, reduced compliance and / or stenosis of the coronary lumen. On this basis, isoproterenol hydrochloride aggravates myocardial ischemia).

[0041] Example 7 TTC staining of myocardial tissue

[0042] After anesthesia, the rats were rapidly excised and washed twice with physiological buffer (PBS) and frozen at -20°C for 30 minutes. The hearts were then removed and evenly cut into three slices. After the slices returned to room temperature, they were placed in PBS containing 1% TTC (2,3,5-Triphenyltetrazolium chloride) and stored in a 37°C incubator protected from light. After 20 minutes, the hearts were removed and flattened on a table for imaging. Image-J software was used to measure and analyze the areas of stained and unstained regions. Red areas represent non-infarcted areas, and white areas represent infarcted areas. A larger ratio of infarcted area to non-infarcted area indicates a more severe infarction.

[0043] All values ​​are expressed as mean ± standard error. Comparisons between two groups were analyzed using the t-test. Comparisons between multiple groups (>2 groups) were analyzed using one-way analysis of variance. A two-sided P value < 0.05 was considered statistically significant.

[0044] result

[0045] 1. Pterostilbene inhibits Orai1 channel-mediated calcium influx in coronary smooth muscle cells

[0046] The experiment used primary cultured SD rat coronary smooth muscle cells. After incubating the cells with a calcium ion fluorescent indicator, the cells were placed in a calcium-free buffer. Pterostilbene was dissolved in DMSO. 1-200 μM pterostilbene was added to the extracellular fluid and incubated for 5 minutes. Then, 2 μM thapsigargin was added to the extracellular fluid to block the calcium pump of the intracellular calcium store, resulting in depletion of the intracellular calcium store and activation of the Orai1 channel. After 5 minutes of treatment, 2 mM Ca was added. 2+ , stimulate calcium store-operated calcium influx, and the experimental results showed that 1-200μM pterostilbene significantly inhibited calcium store-operated calcium influx ( Figure 1 ).

[0047] 2. Pterostilbene inhibits phosphate-induced coronary smooth muscle cell calcification

[0048] The experiment used primary cultured SD rat coronary smooth muscle cells and incubated them with 2% calcification solution (CM: Na2HPO4 and NaH2PO4 in DMEM culture medium, at a ratio of 1:1 so that the final concentration is 3mmol / L) for 0, 5, 7, and 10 days. The experiment was divided into CM group and CM+1μM pterostilbene group. Cell calcification was stained with alizarin red. The results showed that compared with the CM group alone, the alizarin red stained area in the pterostilbene treatment group was significantly reduced ( Figure 2 Another group of cells were divided into CM group and CM + 1μM pterostilbene group. After 10 days of treatment, the cells were lysed and proteins were collected. Western blot was used to detect vascular calcification biomarkers OPN and RUNX2. The results showed that compared with the CM group alone, the expression of OPN and RUNX2 proteins in the pterostilbene treatment group was significantly reduced ( Figure 3 ).

[0049] 3. Pterostilbene significantly inhibits myocardial and coronary artery calcification in calcified rat models

[0050] The experiment used SD rats to prepare a calcification model. After the model was established, the rats were killed and the heart and coronary artery tissues were removed. Compared with the control group (Control), the heart and coronary artery of the calcification group (VC) showed significant white calcification spots ( Figure 4 A); Compared with the VC group, intraperitoneal injection of Synta66 (Orai1 inhibitor) and pterostilbene significantly inhibited the calcification spots in the heart and coronary arteries ( Figure 4 A); however, the inhibitory effect of the positive control drug nifedipine by intraperitoneal injection was not obvious ( Figure 4 A). The coronary artery tissues were stained with alizarin red. The results showed that compared with the control group (Control), the alizarin red staining of the coronary artery tissues of the calcification group animals was significantly enhanced, indicating that the tissue had calcified ( Figure 4B); Compared with the VC group, the Alizarin Red staining of coronary artery tissue in the Orai1 inhibitor Synta66 and pterostilbene intraperitoneal injection treatment groups was significantly weakened, indicating that tissue calcification was significantly inhibited ( Figure 4 B); however, the inhibitory effect of the positive control drug Nifedipine by intraperitoneal injection was not obvious ( Figure 4 B).

[0051] 4. Pterostilbene significantly inhibited the area of ​​acute myocardial ischemia in rats with calcification model

[0052] The experiment used rats with coronary artery calcification and acute myocardial ischemia model. After the model was established, the rats were killed, the hearts were removed, and TTC staining was performed. The results showed that compared with the VC group, intraperitoneal injection of Synta66 (Orai1 inhibitor) and pterostilbene significantly reduced the infarct size. Intraperitoneal injection of nifedipine, a calcium channel blocker for the treatment of myocardial ischemia and a positive control drug, also significantly reduced the myocardial infarct size. Moreover, there were significant differences between the Synta66 or pterostilbene group and the nifedipine group. Therefore, the Synta66 or pterostilbene group showed a stronger effect than the nifedipine group, and there was a significant difference ( Figure 5 ).

[0053] The present invention further claims the use of pterostilbene in the preparation of a medicament for treating coronary artery calcification combined with acute myocardial ischemia. The core invention is the revelation that pterostilbene has a significant therapeutic effect on acute myocardial ischemia induced by a specific pathological context, namely, pre-existing coronary artery calcification (VC), leading to vascular stiffness, reduced compliance, and / or luminal stenosis. Its mechanism of action is to inhibit the progression of vascular calcification, thereby improving vascular function and alleviating the myocardial ischemic damage exacerbated by this underlying pathological condition. This disease type is clearly different from myocardial ischemia-reperfusion disease established by ligation of the left anterior descending coronary artery.

[0054] The present invention focuses on coronary artery calcification combined with acute myocardial ischemia. The construction of this disease model is divided into two steps: first, coronary artery calcification (VC) is induced by specific means (such as high-phosphorus diet, vitamin D induction, etc.), resulting in structural changes in the blood vessels (stiffness, decreased compliance, and lumen stenosis); on this basis, acute myocardial ischemia is induced by intraperitoneal injection of isoproterenol. The core feature of this disease is pre-existing, and the coronary structure and functional disorders caused by calcification are the key basis for inducing and aggravating subsequent myocardial ischemia. The core pathophysiological process of the left anterior descending coronary artery ligation disease model is the inflammatory response damage caused by the sudden interruption of coronary blood flow (ischemia) and then recovery (reperfusion), which is closely related to the Notch1 / eIF3a signaling pathway. The left anterior descending coronary artery ligation disease model does not involve the vascular wall calcification process, nor does it involve the particularity of myocardial ischemia based on chronic vascular calcification lesions.

[0055] The present invention emphasizes that in the context of coronary artery calcification (VC), the stiffness and stenosis of the blood vessels themselves seriously impair the blood flow reserve and oxygen supply capacity of the coronary arteries. On this fragile basis, the sharp increase in myocardial oxygen consumption induced by isoproterenol will exponentially amplify ischemic damage. The therapeutic effect of pterostilbene directly targets the root cause of vascular dysfunction, namely vascular calcification itself. By reducing or delaying the calcification process, improving vascular compliance and lumen patency, the myocardial hypoperfusion caused by calcification is alleviated from the source, thereby reducing the superimposed acute ischemic damage. Its core mechanism is to resist vascular calcification and the resulting improvement in vascular function.

[0056] The above results show that the Orai1 channel inhibitor pterostilbene can significantly inhibit phosphate-induced coronary smooth muscle cell calcification and alleviate acute myocardial infarction in calcification model rats, and its effect in inhibiting myocardial infarction is better than that of the clinical drug nifedipine.

[0057] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. Application of pterostilbene in the preparation of drugs for the treatment of coronary artery calcification.

2. The use according to claim 1, characterized in that The pterostilbene is used as the sole active ingredient in the preparation of the medicine.

3. The use according to claim 1, characterized in that The application of the pterostilbene together with other active ingredients in preparing the medicine.

4. The use according to claim 1, characterized in that The drug is selected from one or more of oral preparations or injections.

5. The use according to claim 5, characterized in that The oral preparation is one or more of capsules, tablets, oral liquids, granules, pills, powders, pills or pastes.

6. The use according to claim 5, characterized in that The injection is administered in one or more of the following ways: subcutaneous administration, intramuscular administration or intravenous administration.

7. A method for inhibiting phosphate-induced coronary smooth muscle cell calcification in vitro, characterized in that: The coronary smooth muscle cells were treated with pterostilbene.

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