The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis

Summary

Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Every year, more than 1 million diabetic patients have amputations, ranking first among non-traumatic amputations.According to the American Diabetes Association (ADA), the incidence of Peripheral Arterial Disease (PAD) in diabetic patients is twice that of non-diabetic patients, and the resulting lower limb ischemia is the main cause of the high mortality and disability rate of diabetic foot.According to the International Working Group on Diabetic Foot (IWGDF), about 50% patients with diabetic foot disease are complicated with PAD, and the degree of vascular stenosis is closely related to the prognosis.Severe limb ischemia is a higher cause of diabetic foot ulcer in China than in western countries.Atherosclerosis is the main pathological change of diabetic peripheral artery disease, and endothelial injury is the initial link of atherosclerosis.Heat shock protein 90 (HSP90) is a kind of important heat stress protein, which accounts for about 2-3% of the total protein in cells.It is involved in the correct folding and activation of intracellular proteins.Although Hsp90 is primarily involved in intracellular protective mechanisms, they can also be exposed to the plasma membrane and released in the extracellular space, resulting in detectable levels of Hsp90 in the blood.Extracellular heat shock proteins are involved in cell-cell communication as well as immune and inflammatory processes.Hsp90 promotes cell survival, migration, inflammation and angiogenesis, and is therefore considered a promising target for cancer therapy.This led to the development of specific HSP90 inhibitors.More recently, these inhibitors have also been tested in diabetic animals.The use of the HSP90 inhibitor 17-DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype in a mouse model with hyperglycemia and hyperlipidemia.Hsp90 is upregulated in human carotid atherosclerotic plaques (especially in unstable areas of plaques) and in patients' serums, triggering autoimmune antibodies against Hsp90 in patients.Is HSP90 also present in serum of patients with diabetic peripheral arterial disease?Is there a relationship between secretory heat shock protein 90 and arterial disease?The study that HSP90 may be involved in the molecular mechanism of vascular endothelial barrier function impairment in diabetes will provide a new target for the early serological diagnosis and treatment of diabetic vascular disease.The aim of this study was to investigate the relationship between the degree of vascular disease and serum heat shock protein 90 in patients with type 2 diabetes.The study was divided into three groups: diabetic without PAD group, diabetic with PAD group and diabetic foot group.According to the degree of peripheral artery disease, the patients were divided into three groups, and the content of heat shock protein 90 in serum of the patients was detected.To analyze the correlation between the degree of peripheral arterial disease and the content of heat shock protein 90 in serum.

Conditions

• Peripheral Arterial Disease

Interventions

OTHER

non-intervention

non-intervention

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University

  lead OTHER

Principal Investigators

• Mengchen Zou · labor relations

Eligibility

Min Age

40 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-09-01

Primary Completion

2020-11-10

Completion

2020-12-10

Countries

• China

Study Locations