Targeting the Endothelium to Achieve Cardioprotection

Herrera-Zelada, Nicolas; Zúñiga-Cuevas, Úrsula; Ramírez-Reyes, Andrés; Lavandero, Sergio; Riquelme, Jaime A.

doi:10.3389/fphar.2021.636134

Cited by 18 publications

(15 citation statements)

References 168 publications

(223 reference statements)

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“…Endothelial cells have been identified as a therapeutic target for treating MI and preventing the progression to heart failure. [55,56] Angiogenesis has been shown to be negatively impacted by MG accumulation, in part through the up-regulation of antiangiogenic factors and dysregulation of VEGF signaling. [57,58] Our in vitro results showed that fisetin-HG can prevent MGinduced defective angiogenesis in cultured endothelial cells, and we observed an increase in arteriole density in the MI mouse model after fisetin-HG treatment.…”

Section: Discussionmentioning

confidence: 99%

Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post‐Myocardial Infarction

Çimenci

Blackburn

Sedláková

et al. 2021

Adv Funct Materials

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Methylglyoxal (MG) is a highly reactive dicarbonyl and the main precursor of advanced glycation end-products (AGEs). After myocardial infarction (MI), MG-derivedAGEs accumulate in the heart and contribute to adverse remodeling and loss of cardiac function. In this study, the flavonoid fisetin, a dicarbonyl scavenger, is used to reduce the negative effects of MG in the post-MI heart. A fisetin-loaded collagen type I hydrogel (fisetin-HG) is injected intramyocardially in mice at 3 h post-MI, and compared to fisetin-alone, hydrogel-alone, or saline treatment. Fisetin-HG treatment increases the level of glyoxalase-1 (the main MG-metabolizing enzyme), reduces MG-AGE accumulation, and decreases oxidative stress in the MI heart, which is associated with smaller scar size and improved cardiac function. Treatment with fisetin-HG also promotes neovascularization and increases the number of pro-healing macrophages in the infarct area, while reducing the number of pro-inflammatory macrophages.Taken together, the results demonstrate that the fisetin-collagen hydrogel therapy can reduce the accumulation and negative effects of MG post-MI. This therapy may be a promising approach to limit adverse cardiac remodeling, prevent damage, and preserve function of the infarcted heart.

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Section: Discussionmentioning

confidence: 99%

Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post‐Myocardial Infarction

Çimenci

Blackburn

Sedláková

et al. 2021

Adv Funct Materials

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“…The above evidence, however, suggests that vascular ECs undergo angiogenesis by EVs. Furthermore, endothelialderived EVs could directly contribute to transduce RIC into a proangiogenic output [60]. Early work demonstrated that cultured HUVECs shed EVs, ranging from 300 to 600 nm and containing matrix metalloprotease-2 (MMP-2) and MMP-9, which autocrinally stimulate endothelial migration [61].…”

Section: Endothelium Evs and Angiogenesismentioning

confidence: 99%

Extracellular vesicles (EVs) in ischemic conditioning and angiogenesis: Focus on endothelial derived EVs

Alfì

Thairi

Femminò

et al. 2021

Vascular Pharmacology

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During myocardial ischemia, timely reperfusion is critical to limit infarct area and the overall loss of cardiac contractile function. However, reperfusion further exacerbates the damage of the ischemic heart. This type of injury is known as ischemia-reperfusion injury (IRI). Ischemic conditioning is a procedure which consists of brief cycles of ischemia and reperfusion in order to protect the myocardium against IRI. Remote ischemic conditioning (RIC), namely transient brief episodes of ischemia at a remote site before a subsequent damaging ischemia/ reperfusion procedure of the target organ (e.g., the heart), protects against IRI. However, how the stimulus of RIC is transduced from the remote organ to the ischemic heart is still unknown. Recently, extracellular vesicles (EVs) have been proposed to have a role in the RIC procedure. The endothelium releases EVs and is also one of the tissues mostly exposed to EVs during their journey to the target organ. Moreover, EVs may have important roles in angiogenesis and, therefore, in the remodeling of post-ischemic organs. Here we analyze how EVs may contribute to the overall cardioprotective effect and the implication of the endothelium and its EVs in RIC mediated acute cardioprotection as well as in angiogenesis.

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“…In addition, increased endothelial permeability and excessive cellular swelling represent critical mechanisms of MIRI. Therefore, endothelial cells are becoming a vital target of multiple therapeutic approaches to MIRI in diabetes [9].…”

Section: Introductionmentioning

confidence: 99%

Resolvin D1 inhibits endothelial permeability and mitochondrial damage following cardiac ischemia reperfusion in diabetic mice

Zhang

Huang

Chen

et al. 2021

Preprint

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Purpose Novel strategies for preventing myocardial ischemia reperfusion injury (MIRI) in a diabetic heart are urgently needed. Resolvin D1 (RvD1) plays important therapeutic roles in inflammatory diseases. However, the therapeutic role of RvD1 in diabetic MIRI is still unknown. Methods Diabetic mice were established with a high-fat diet and streptozotocin (STZ). The mice were pretreated with RvD1 via intraperitoneal injection for 3 days, followed by MIRI. To evaluate the effects of RvD1 on chronic cardiac remodelling, RvD1 was administered for another 2 weeks after MIRI. The effects of RvD1 following MIRI were measured, including the severity of infarct size, regional inflammation, cardiac function, and permeability of cultured endothelial monolayers. Mitochondrial reactive oxygen species (MitoROS) and mitochondrial membrane potential (MMP) were determined using MitoSOX and JC-1. Results RvD1 pretreatment significantly reduced infarct size and the Evans blue content in diabetic injured hearts, which was associated with improved endothelial permeability. At 2 weeks after MIRI, RvD1 treatment partially improved cardiac performance and reduced cardiac fibrosis in diabetic MIRI mice. In vitro, RvD1 attenuated endothelial leakage induced by hypoxia-reoxygenation, H2O2, and lipopolysaccharide (LPS) under high glucose (HG) conditions. Meanwhile, RvD1 remarkably protected endothelial cells from H2O2-induced mitochondrial damage, as evidenced by increased MMP and decreased MitoROS, which was associated with the preservation of VE-cadherin. Conclusion RvD1 alleviates MIRI-induced endothelial permeability and mitochondrial damage injuries in diabetic hearts. Therefore, RvD1 could be a potential therapeutic target for MIRI in diabetes.

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Targeting the Endothelium to Achieve Cardioprotection

Cited by 18 publications

References 168 publications

Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post‐Myocardial Infarction

Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post‐Myocardial Infarction

Extracellular vesicles (EVs) in ischemic conditioning and angiogenesis: Focus on endothelial derived EVs

Resolvin D1 inhibits endothelial permeability and mitochondrial damage following cardiac ischemia reperfusion in diabetic mice

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