Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction

Zeng, Heng; Chen, Jianxiong

doi:10.3389/fcvm.2019.00015

Cited by 53 publications

(46 citation statements)

References 73 publications

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“…Impaired vessel formation is still considered a relevant mechanism in abnormal vascular remodelling in these clinical settings 33 . Moreover, (micro)vessel dysfunction and vessel regression/rarefaction combined with poor neovascularization contribute to pathophysiology of systemic metabolic syndrome/diabetic heart failure 34 . Therefore, boosting the neovascularisation of damaged tissues remains necessary for the improvement of patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

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Serum-derived extracellular vesicles (sEV) from healthy donors display in-vivo pro-angiogenic properties. To identify patients that may benefit from autologous sEV administration for pro-angiogenic purposes, sEV angiogenic capability has been evaluated in type 2 diabetic (T2DM) subjects (D), in obese individuals with (OD) and without (O) T2DM, and in subjects with ischemic disease (IC) (9 patients/ group). sEV display different angiogenic properties in such cluster of individuals. miRNomic profile and tGfβ content in sEV were evaluated. We found that miR-130a and TGFβ content correlates with sEV in-vitro and in-vivo angiogenic properties, particularly in T2DM patients. Ingenuity Pathway Analysis (IPA) identified a number of genes as among the most significant miR-130a interactors. Gain-of-function experiments recognized homeoboxA5 (HOXA5) as a miR-130a specific target. Finally, ROC curve analyses revealed that sEV ineffectiveness could be predicted (Likelihood Ratio+ (LH+) = 3.3 IC 95% from 2.6 to 3.9) by comparing miR-130a and TGFβ content 'in Series'. We demonstrate that sEV from high cardiovascular risk patients have different angiogenic properties and that miR-130a and TGFβ sEV content predicts 'true ineffective sEVs'. These results provide the rationale for the use of these assays to identify patients that may benefit from autologous sEV administration to boost the angiogenetic process. Cardiovascular complications are relevant causes of morbidity and mortality in patients with diabetes and obesity 1. Recent evidence suggests that extracellular vesicles (EVs) may act as mediators of many pathophysiological processes 2-4. EVs are small vesicles that are released from different cell types under normal and pathological conditions 5,6. Increased levels of circulating EVs have been associated with vascular impairment and hypercoagulability, particularly in patients with diabetes and acute coronary syndrome, suggesting that they play a role in driving cardiovascular diseases 7,8. Moreover, increased levels of circulating EVs, mainly from platelets and endothelial cells, has been proposed as a hallmark of cell dysfunction 9. It has been extensively reported that EVs act as biological active vectors, and participate in the exchange of information between circulating and resident cells, including endothelial cells 2,10. It has also been proposed that platelet-derived EVs play a role in the pathogenesis of atherosclerosis 11. EVs act as biological intermediaries, and mainly do so by delivering proteins, active lipids and extracellular RNAs 12. However, the most frequently studied EV-mediated biological processes rely on microRNA (miRNA) transfer. miRNAs are a class of small noncoding RNAs post-transcriptionally regulating gene expression 13. miR-NAs are present in serum/plasma and it has been proposed that their distinctive expression patterns serve as disease fingerprints in many clinical settings 14. Moreover, it has been shown that activated platelets can transfer

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Section: Discussionmentioning

confidence: 99%

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Cavallari

Figliolini

Tapparo

et al. 2020

Sci Rep

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show abstract

“…It is associated with hypertension (58, 59), hypertrophy (60), diabetes (61), and aging in multiple tissues in both men and women (62). Coronary microvascular rarefaction was shown to be a prominent cause of HFpEF in male and female patients (63, 64). However, mechanisms underlying coronary rarefaction are not fully understood, but are likely comparable to those in other circulatory organs, such as the kidneys.…”

Section: Capillary Rarefactionmentioning

confidence: 99%

Estrogen Contributions to Microvascular Dysfunction Evolving to Heart Failure With Preserved Ejection Fraction

et al. 2019

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Heart failure with preserved ejection fraction (HFpEF) is a syndrome involving microvascular dysfunction. No treatment is available yet and as the HFpEF patient group is expanding due to the aging population, more knowledge on dysfunction of the cardiac microvasculature is required. Endothelial dysfunction, impaired angiogenesis, (perivascular) fibrosis and the pruning of capillaries (rarefaction) may all contribute to microvascular dysfunction in the heart and other organs, e.g., the kidneys. The HFpEF patient group consists mainly of post-menopausal women and female sex itself is a risk factor for this syndrome. This may point toward a role of estrogen depletion after menopause in the development of HFpEF. Estrogens favor the ratio of vasodilating over vasoconstricting factors, which results in an overall lower blood pressure in women than in men. Furthermore, estrogens improve angiogenic capacity and attenuate (perivascular) fibrosis formation. Therefore, we hypothesize that the drop of estrogen levels after menopause contributes to myocardial microvascular dysfunction and renders post-menopausal women more vulnerable for heart diseases that involve the microvasculature. This review provides a detailed summary of molecular targets of estrogen, which might guide future research and treatment options.

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“…Coronary microvascular rarefaction leads to decreased coronary flow reserve and microvascular ischaemia. Although CMR is not able to directly quantify coronary microvascular density, it can measure its consequences, in terms of reduced coronary flow reserve (perfusion studies) and increased fibrosis (T1 mapping) 48,54 …”

Section: Microvasculaturementioning

confidence: 99%

Cardiac magnetic resonance in heart failure with preserved ejection fraction: myocyte, interstitium, microvascular, and metabolic abnormalities

Quarta

Gori

Iorio

et al. 2020

European J of Heart Fail

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Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes-with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

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Microvascular Rarefaction and Heart Failure With Preserved Ejection Fraction

Cited by 53 publications

References 73 publications

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential

Estrogen Contributions to Microvascular Dysfunction Evolving to Heart Failure With Preserved Ejection Fraction

Cardiac magnetic resonance in heart failure with preserved ejection fraction: myocyte, interstitium, microvascular, and metabolic abnormalities

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