BACKGROUND

Field

The present invention relates to a composition for treating a vascular smooth muscle cell proliferative disease, a composition for diagnosing the same, and a method for detecting a diagnostic marker and, more specifically, to a composition for treating a vascular smooth muscle cell proliferative disease, the composition comprising, as an active ingredient, a recombinant expression vector comprising a polynucleotide encoding FGF12 or FGF12 protein or a fragment thereof; to a composition for diagnosing a vascular smooth muscle cell proliferative disease, the composition comprising an agent for measuring the expression level of FGF12 mRNA or FGF12 protein; and to a method for detecting a marker for a vascular smooth muscle cell proliferative disease using the same.

Discussion of the Background

Vascular smooth muscle cells form and support vascular structures and are very important in repeating relaxation and contraction through the regulation of autonomic nervous systems and hormones to achieve smooth blood circulation. Vascular smooth muscle cells highly express smooth muscle-specific genes, such as SMA, SM22α, SM-MHC, SM-calponin, and desmin and hardly proliferate in a healthy and normal condition, but actively proliferate and migrate, as a part of a remodeling procedure for restoring vascular injury in a situation where vascular injury due to vascular wounds, atherosclerosis, inflammation, or other vascular diseases needs to be restored. When the proliferation of vascular smooth muscle cells is not normally regulated and occurs excessively due to abnormal signaling or repetitive injury, smooth muscle cells migrate from the medial layer as the original position to the intima layer and continue to proliferate, thereby forming the neointimal layer, and the involvement of inflammation or thrombus formation results in the occurrence of diseases, such as pulmonary arterial hypertension and vascular stenosis including vascular wall thickening and vessel lumen narrowing.

The current treatment of vascular stenosis is mainly carried out by surgical procedures, such as stent procedures or angioplasty, while these procedures also injure blood vessels and thus have a high probability of recurrence. The stent procedures using the treatment with an anti-platelet agent, an anti-coagulant, an anti-allergic agent, or a drug inhibiting tissue regeneration have been clinically attempted to prevent or treat vascular stenosis, but these procedures do not sufficient treatment effects. Therefore, a fundamental medicine capable of inhibiting the proliferation of smooth muscle cells to treat vascular stenosis and a diagnostic reagent capable of diagnosing the prognosis of diseases and treatment thereof need to be developed.

Of the above-exemplified diseases accompanied by smooth muscle cell proliferation, especially pulmonary arterial hypertension (PAH) has no distinctive symptoms or signs from other diseases, and thus early diagnosis thereof is difficult, while PAH progresses slowly, and thus the time from initial symptoms to definite diagnosis is long, resulting in a high mortality rate. Pulmonary arterial hypertension is a condition in which the blood pressure of the pulmonary artery that supplies blood from the heart to the lungs is increased, resulting in degraded blood circulation, and defined as a state in which the mean pulmonary artery pressure is 25 mmHg or more. The initial symptoms of the disease are not detected, but as the disease progresses, the cardiac output decreases due to overload of the heart in which the blood needs to be released to the lungs through the narrowed pulmonary blood vessels. As a result, dyspnea during exercise, fatigue, general weakness, dizziness, and the like occur, and symptoms, such as hemoptysis, angina, chest pain, and leg edema, may develop, and in severe cases, the symptoms may lead to fainting or heart attack. The pulmonary arterial hypertension is a rare disease that occurs at a rate of 2-10 per million people, but the actual number of patients is expected to be greater considering that the diagnosis thereof is difficult, while the pulmonary arterial hypertension is an intractable disease with a mortality rate of 15% within one year and 50% or more after five years. On the contrary, the treatment strategies remain in symptomatic therapy for alleviating symptoms, while effective medicines and treatment methods are very few.

Therefore, the development of effective diagnostic reagents capable of achieving early diagnosis of diseases caused by excessive proliferation of smooth muscle cells, including pulmonary arterial hypertension, and therapeutic agents therefor is urgent.

The present inventors, while researching proliferation procedures of smooth muscle cells, found that the expression level of FGF12 is closely associated with the proliferation of vascular smooth muscle cells, and especially confirmed that the expression of FGF12 is reduced in the injured blood vessels in which the proliferation of smooth muscle cells actively occurs, and the excessive expression of FGF12 in the injured blood vessels inhibited the proliferation of smooth muscle cells, and therefore, the present inventors completed the present invention.

SUMMARY

The present disclosure provides a method for treating a smooth muscle cell proliferative disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a recombinant expression vector comprising a polynucleotide encoding FGF12.

In another aspect, the present disclosure provides a method for treating a smooth muscle cell proliferative disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising FGF12 protein or a fragment thereof.

In still another aspect, the present disclosure provides a method for detecting a marker for a smooth muscle cell proliferative disease, the method, in order to provide information necessary for diagnosis of the smooth muscle cell proliferative disease, comprising:

(a) providing a sample of a subject to be detected;

(b) measuring the expression level of FGF12 in the sample; and

(c) comparing the measured expression level of FGF12 with that of a normal subject and determining that the subject is considered to have been afflicted with a smooth muscle cell proliferative disease or to have a probability of being afflicted with a smooth muscle cell proliferative disease in case where the subject has a reduced FGF12 expression level compared with the normal subject.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.

