The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis

NCT04787770 | Completed DMC

• 1 other identifier: NFEC-2020-268
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

diabetic disease; peripheral arterial disease; Extracellular heat shock protein 90

Outcome Measures

Primary Outcomes (1)

• Heat shock protein 90

  The serum heat shock protein 90 was detected

  In December 2020

Study Arms (3)

diabetes without complications

diabetes without complications

Other: non-intervention

diabetes with Peripheral Arterial Disease

diabetes with Peripheral Arterial Disease

Other: non-intervention

diabetic foot group

diabetic foot group

Other: non-intervention

Interventions

non-intervention OTHER

non-intervention

diabetes with Peripheral Arterial Disease; diabetes without complications; diabetic foot group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

150 cases, 50 cases in each group.

You may qualify if:

• Diagnostic criteria for diabetes: using WHO1999 diabetes diagnostic criteria, that is, (1) having diabetes symptoms (polyuria, polydipsia, and unexplained weight loss), and random (any time after meal) plasma glucose ≥11.1mmol/L(200mg/ dL);(2), or fasting (fasting for at least 8 hours) plasma glucose ≥7.0mmol/L(126mg/ dL);(3), or OGTT 2 hours plasma glucose ≥11.1mmol/L(200mg/ dL)
• Agree to participate in the study and data collection, and sign the informed consent.

You may not qualify if:

• \. Diabetic ketoacidosis or hyperosmolar state occurs within 30 days; Diabetic coma in 2 or 3 months, or severe hypoglycemia in nearly 1 month; 3. Diseases of tumor, immune system and hematopoietic system; 4. Other types of diabetes 5. Less than 40 years old

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

Related Publications (1)

• Ding X, Meng C, Dong H, Zhang S, Zhou H, Tan W, Huang L, He A, Li J, Huang J, Li W, Zou F, Zou M. Extracellular Hsp90alpha, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes. BMJ Open Diabetes Res Care. 2022 Jan;10(1):e002579. doi: 10.1136/bmjdrc-2021-002579.

  PMID: 35091448 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Mengchen Zou

  labor relations

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 9, 2021
• Study Start: September 1, 2020
• Primary Completion: November 10, 2020
• Study Completion: December 10, 2020
• Last Updated: March 9, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)