Exercise-Induced Modulation of Atherosclerosis Mechanisms

Regular physical exercise exerts a multifaceted protective effect against atherosclerosis by modulating lipid handling, vascular inflammation and endothelial homeostasis. Sustained aerobic or resistance training enhances high-density lipoprotein-mediated reverse cholesterol transport and reduces low-density lipoprotein deposition within the arterial wall. Concurrently, exercise upregulates endothelial nitric oxide synthase, boosting nitric oxide bioavailability to preserve vasodilatory capacity and attenuate oxidative stress. Skeletal muscle contraction induces PPARγ coactivator-1α expression, driving the release of myokines that suppress vascular cell adhesion molecule levels and monocyte infiltration. Moreover, habitual exercise mitigates endoplasmic reticulum stress and inflammasome activation in endothelial cells via enhanced uncoupling protein 2 activity, leading to improved coronary microvascular function. These interconnected mechanisms collectively stabilise plaques, reduce arterial stiffness and lower overall cardiovascular risk.

Research from Nature Portfolio

Recent studies have shown that aerobic exercise training in female murine models counteracts age-associated cardiac and autonomic disturbances in atherosclerosis, restoring diastolic function, normalising heart-rate variability and reducing aortic wall thickening. Further work in apolipoprotein-E knockout mice demonstrates that routine treadmill exercise alleviates coronary endothelial dysfunction by downregulating endoplasmic reticulum stress proteins, enhancing uncoupling protein 2 expression and augmenting nitric oxide production, while simultaneously suppressing NLRP3 inflammasome signalling and vascular superoxide generation.

Exercise-Induced Modulation of Atherosclerosis Mechanisms publication trend

The graph below shows the total number of articles in exercise-induced modulation of atherosclerosis mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Atherosclerosis: A chronic arterial disease characterised by lipid accumulation, inflammatory cell infiltration and fibrous tissue formation within the vessel wall.

Endothelial dysfunction: Impaired endothelium-dependent vasodilation resulting from reduced nitric oxide bioavailability and elevated oxidative stress.

Reverse cholesterol transport: The process by which cholesterol is effluxed from peripheral cells, particularly macrophages, and transported to the liver for excretion.

Endoplasmic reticulum (ER) stress: A cellular condition arising from accumulation of misfolded proteins in the ER, triggering adaptive and inflammatory signalling cascades.

Uncoupling protein 2 (UCP2): A mitochondrial inner-membrane protein that modulates reactive oxygen species production and supports endothelial function under stress.

PPARγ coactivator-1α (PGC-1α): A transcriptional coactivator upregulated by exercise that drives mitochondrial biogenesis and myokine secretion in skeletal muscle.

References

1. Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis. Scientific Reports (2024).
2. Reverse Cholesterol Transport: Molecular Mechanisms and the Non-medical Approach to Enhance HDL Cholesterol. Frontiers in Physiology (2018).
3. Skeletal Muscle-specific PGC-1α Overexpression Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice. Scientific Reports (2019).
4. Exercise training mitigates ER stress and UCP2 deficiency-associated coronary vascular dysfunction in atherosclerosis. Scientific Reports (2021).
5. Aerobic exercise training protects against endothelial dysfunction by increasing nitric oxide and hydrogen peroxide production in LDL receptor-deficient mice. Journal of Translational Medicine (2016).
6. The Complementary Effects of Atorvastatin and Exercise Treatment on the Composition and Stability of the Atherosclerotic Plaques in ApoE Knockout Mice. PLOS ONE (2014).