The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis
Condition: Peripheral Arterial Disease
MeSH terms: Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
Study type: Observational

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.
    

Detailed description: 
      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.

        1. Serum collection: the nurses collected the patients' fasting blood at 6:00 am in
           accordance with the routine blood collection procedures: 1 tube of procoagulant blood
           and 1 tube of anticoagulant blood were collected, each tube was no less than 3ml of
           blood;Store in a 4-degree refrigerator for disposal.

        2. Collection of serum and plasma: the blood samples collected by the nurse were placed in
           a centrifuge, centrifuged at 3000 RPM for 15 minutes, and then the supernatant was
           collected.

        3. Laboratory test: the collected serum or plasma were quantitatively tested by HSP90
           ELISA, and the results were analyzed.The remaining serum or plasma was stored in a
           negative 80 refrigerator.
    

Intervention name(s): non-intervention
Intervention type(s): Other
Intervention description(s): non-intervention
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        150 cases, 50 cases in each group.
      
Keywords: diabetic disease; peripheral arterial disease; Extracellular heat shock protein 90