From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1
Abstract
:1. Introduction
2. Regulation of Microcirculation by Endothelial SIRT1
2.1. Regulation of Physiological Capillarization by SIRT1
2.2. SIRT1 and Diabetic Microangiopathy
2.3. SIRT1, Oxidative Stress and Mitochondrial Function
2.4. SIRT1 and Coronary Microvascular Function
2.5. SIRT1 and Brain Microvascular Function
3. Mechanisms Underlying Regulation of Microcirculation by Endothelial SIRT1
3.1. SIRT1 Enhances Endothelium-Dependent Vasodilation in an eNOS-Dependent Manner
3.2. Anti-Senescence Activity of Endothelial SIRT1
3.2.1. SIRT1-NF-κB Interaction Dictates Microvascular Function and Inflammation
3.2.2. Senescence, Autophagy and SIRT1
3.2.3. SIRT1-PARP Has a Bidirectional Interaction in Regulating Microvascular Function
3.2.4. SIRT1 Regulates Oxidative Stress and Mitochondrial Dysfunction
3.3. SIRT1 Plays a Dual Role in Micro-Neovascularization
3.3.1. SIRT1 Promotes Angiogenesis by Inhibiting DLL4-Notch Signaling
3.3.2. SIRT1 Suppresses HIF-1α-Induced Pathological Angiogenesis
3.3.3. SIRT1-eNOS Axis Promotes Tissue Capillarization
3.4. SIRT1 Upregulates Tight Junction Proteins to Maintain Micro-Endothelial Cell-Cell Junctions
3.5. SIRT1 and Microcirculatory Thrombosis
3.5.1. SIRT1 Regulates Endothelial Glycocalyx Function
3.5.2. SIRT1 Interacts with Prostacyclin Signaling
3.5.3. SIRT1 Directly Regulates Platelet Activity and Lifespan
4. Targeting Microvascular SIRT1 in Aging-Related Disease
4.1. Natural Modulators of SIRT1
4.1.1. Resveratrol
4.1.2. Other Natural Modulators
4.2. Endogenous SIRT1 Modulators
4.2.1. Nicotinamide Adenine Dinucleotide (NAD+) Modulators
4.2.2. Hormones and Hormone-like Substances
4.2.3. Non-Coding RNA (ncRNA) Modulators of SIRT1
MicroRNA (miR)
Circular RNA (circRNA)
Long Non-Coding RNA
tRNA-Derived Stress-Induced RNA (tiRNAs)
4.3. Synthetic SIRT1 Modulators
4.3.1. SRT1720
4.3.2. SIRT1 Inhibitors
4.3.3. Other SIRT1 Modulators
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Natural SIRT1 Intervention | Primary Mechanisms | Reference |
---|---|---|
Boysenberry polyphenols | Enhanced capillarization and BAT function, increased systemic glucose tolerance, and optimized thermogenesis. | [13] |
Lycopene | Increase skeletal muscle capillary density, prevent MEC damage | [22] |
Stachydrine | Inducing RMEC autophagy, suppressing ROS and inflammation, | [46] |
Ligustrazine | Promote angiogenesis of BMECs while suppressing CMD, platelet activation, inflammation, and coronary micro-embolization | [54,176] |
14,15 epoxyeicosatreinoic acid | Promote mitophagy | [67] |
Hydroxysafflor Yellow A | Promote BBB integrity, angiogenesis, and survival of BMECs | [66,175] |
Coumestrol | Suppressing inflammation, oxidative stress, and apoptosis in human RMECs | [172] |
Wogonoside | Suppressing abnormal angiogenesis, permeability, proliferation, and migration of RMECs | [173] |
Safranal | Promote survival, proliferation, and angiogenesis in BMECs | [174] |
Salvianolic acid B | Promote anti-inflammatory M2 macrophage polarization, angiogenesis, muscle capillary density, and blood perfusion. | [177] |
NAD+ Modulating Intervention | Primary Mechanisms | Reference |
---|---|---|
Sodium hydrosulfide+ NMN | Synergistic SIRT1 activation, promoting exercise-induced capillarization of skeletal muscle | [17] |
Nicotinamide mononucleotide (NMN) | Promote angiogenesis and suppress ROS production in CMECs, and increase exercise-induced skeletal muscle capillary density | [17,77] |
Recombinant human nicotinamide mononucleotide adenylyl transferase | Enhanced BBB integrity | [63] |
Nicotinamide riboside | Prevent intestinal MEC dysfunction and reduce ROS production under inflammatory conditions | [89] |
S-propargyl-cysteine | Promote endogenous H2S production, upregulating SIRT1 and microvascular reconstruction following peripheral nerve injury | [135] |
MicroRNA (miR) | Effect on SIRT1 and Microcirculation | Reference |
---|---|---|
miR-29 | Inhibits SIRT1, but is induced by regular exercise and associated with increased antioxidant activity and reduced endothelial dysfunction. | [18,188] |
miR-377 | Inhibit SIRT1 expression aggravates cell cycle transition, angiogenesis, migration, and inflammation in human RMECs under HG conditions. | [27] |
miR-195 | Increased under diabetic condition. In RMECs, inhibit SIRT1 expression, increasing apoptosis and reducing proliferation. In CMECs, reduced SIRT1 impairs myocardial function, causing oxidative stress and myocardial hypertrophy | [35,185] |
miR-30b | Negatively regulate SIRT1, promoting pathological angiogenesis in proliferative diabetic retinopathy. | [38] |
miR-221 | Inhibit SIRT1/Nrf2 signaling in human RMECs, promoting apoptosis under HG conditions. | [42] |
miR-34a-5p | Suppress SIRT1 in CMECs induces platelet activation, inflammation, and CMD. | [54] |
miR-16-5p | Inhibition of miR-16-5p downregulates SIRT1, exacerbating cerebral infarction in mice. | [65] |
miR-145 | Inhibit SIRT1, inducing NF-kB mediated inflammation, autophagy, and lung injury in a pulmonary I/R model. | [103] |
miR-141-3p | Ameliorated lung injury by inhibit SIRT1-induced pulmonary MEC beclin-1-dependent autophagy in mice pulmonary H/R model. | [114] |
miR-34a | Decrease SIRT1 levels, diminish mitochondrial function antioxidant capacity, and induce senescence in human RMECs under HG conditions. | [129] |
miR-29b-3p | Downregulate SIRT1, decrease human RMEC viability, and upregulate apoptosis under HG conditions. | [186] |
miR-92a | Inhibition of miR-92a induced SIRT1 expression and induced angiogenesis in subcutaneous tissue, elevating capillary density in a chicken chorioallantoic membrane model. | [187] |
miR-126 | Promote SIRT1/Nrf2 signaling, and attenuate oxidative/inflammatory response to OGD/R injury in HUVECs. | [189] |
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Law, M.; Wang, P.-C.; Zhou, Z.-Y.; Wang, Y. From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1. Pharmaceuticals 2024, 17, 1495. https://doi.org/10.3390/ph17111495
Law M, Wang P-C, Zhou Z-Y, Wang Y. From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1. Pharmaceuticals. 2024; 17(11):1495. https://doi.org/10.3390/ph17111495
Chicago/Turabian StyleLaw, Martin, Pei-Chun Wang, Zhong-Yan Zhou, and Yu Wang. 2024. "From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1" Pharmaceuticals 17, no. 11: 1495. https://doi.org/10.3390/ph17111495
APA StyleLaw, M., Wang, P. -C., Zhou, Z. -Y., & Wang, Y. (2024). From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1. Pharmaceuticals, 17(11), 1495. https://doi.org/10.3390/ph17111495