Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04743128 |
| Other study ID # |
HSP 70 CLPQ |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 3, 2019 |
| Est. completion date |
August 30, 2019 |
Study information
| Verified date |
April 2022 |
| Source |
Universidad Popular Autónoma del Estado de Puebla |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Introduction: Atherosclerotic Peripheral Arterial Disease (PAD) is the leading cause of
mortality in the western world. To maintain homeostasis of the vessel wall, vascular cells
produce a high level of heat shock proteins (HSP), among which is Hsp70, to stimulate innate
immunity and face stress.
Methods: This is a clinical trial where 260 individuals were evaluated by a screening test
employing the Ankle-Arm Index (ABI), 220 of them were not within risk value (0.91 to 0.99
mmHg). In the clinical trial, 32 individuals were included. A control group and an
experimental group were formed. Aerobic exercise intervention was performed for 12 weeks. The
level of Hsp70 was evaluated, physical and clinical measurements were applied at the
beginning and at the end of the trial.
Description:
The objective of the study is to determine the level of serum expression of the HSP70 protein
in individuals at risk of atherosclerotic peripheral arterial disease, after an intervention
of moderate exercise.
Atherosclerotic Peripheral Arterial Disease (PAD) is a systemic disease that causes
obstruction of arterial blood flow and is a significant cause of morbidity and mortality
worldwide 1.
Patients with PAD have a three times greater risk of myocardial infarction, stroke and death
than those without the disease. However, more than 50% of patients are asymptomatic; so the
disease remains underdiagnosed. 2 It is estimated that 202 million people in the world are
affected with PAD, 45 million of them die from coronary or cerebrovascular disease in a range
of ten years. The current prevalence of PAD in Mexico is 10% of the general population.3 The
disease is strongly related to modifiable risk factors (blood pressure, sedentary lifestyle,
baseline glycemia, cholesterol, and obesity) and unhealthy lifestyle (tobacco, physical
inactivity, food and psychosocial stress), which increases the risk of acquiring the disease
up to 17.2 times 4, 5, 6 Increased membrane permeability leads to the accumulation and
modification of proteins, lipids and lipoproteins in the endothelium. The accumulation of
pro-inflammatory molecules such as chemo-tactical monocyte protein 1 (MCP-1), intracellular
adhesion molecules (ICAM-1), vascular cell adhesion (VCAM-1) and higher nitro-tyrosine
content are also generated. 7 Macrophages are active in response to the spread of the
inflammatory response and bind to low-density lipoprotein (LDL) receptors that had
internalized.
Macrophages secrete pro-inflammatory cytokines resulting in the recruitment and activation of
additional immune cells at the site of the lesion, amplifying the immune response and
promoting the development of complex and advanced plaques that become mature atherosclerotic
plaques.8 The Ankle Arm Index (ABI) is the non-invasive gold standard accepted for both the
diagnosis and evaluation of the severity of this disease. The cut-off point for the diagnosis
of PAD is an ABI of less than 0.90 at rest, regardless of the Framingham Risk Score, being
95% sensitive in the detection of PAD. 9, 10 To maintain homeostasis on the vessel wall,
vascular cells produce a high level of heat shock proteins (HSP) 11. These types of stress
proteins are cytoprotective agents that promote cell survival during stressors. 12 The
reduction of HSP intracellular expression is also related to PAD, cardiovascular diseases and
metabolic syndrome, where they are greatly diminished. 10 HSP are normally intracellular
proteins, but when released at an extracellular level, they exert an immune response.13 The
most thermo-sensitive and highly inducible HSP belongs to the 70 kilodalton (kDa) family, as
established by Mizzen et al., In 1998 (figure 1). It is believed that extracellular Hsp70
(eHsp70) stimulates innate immunity and acts as a danger signal. Serum Hsp70 has been
detected in the peripheral circulation of apparently healthy individuals and increases in
response to different stressors, including exercise. 12, 14
Figure 1. Schematic representation of the molecular structure of HSP70. Adapted from Carrasco
L. et al. 15 Exercise increases HSP levels primarily through reactive oxygen species (ROS),
elevated temperature, hormones, calcium fluxes or mechanical tissue deformation.16 It has
been shown that the concentration of Hsp70 increases after performing both acute and
long-term exercises, reaching levels that remain high, but once its protective action
decreases both at intra and extra-cellular levels.17 Exercise exerts beneficial effects
against atherosclerosis by increasing circulating endostatin, which inhibits the development
of atherosclerotic plaque by blocking angiogenesis in plaque tissue.18 Isotonic contractions
of the type of resistance exercise (aerobic) tend to lead to increases in Hsp70 levels, as
opposed to eccentric exercise. With repetitive exercise, an induced increase in this protein
is maintained, while the initial response of other HSPs to exercise decreases as training
progresses.16 Regular exercise initiates long-term processes of adaptation of muscle
metabolism, cardiovascular system and immuno-modulatory effects that are largely considered
beneficial; There is evidence that during exercise, Hsp70 is released into human circulation
in association with exosomes, specifically with aerobic exercise.19, 20 It has been shown
that Hsp70 directly inhibits inflammatory processes through the suppression of oxidative
stress, directly reduces apoptosis, hyperplasia, as well as decreasing the expression of
adhesion molecules that lead to leukocyte extravasation and the manifestation of inflammatory
cytokines.16 Higher serum levels of Hsp70 are associated with reduced thickening of the
atherosclerotic intima and a lower risk of coronary artery disease.21
