Mitochondrial Dysfunction in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Opportunities

Gallo, Giovanna; Rubattu, Speranza; Volpe, Massimo

doi:10.3390/ijms25052667

Cited by 13 publications

(1 citation statement)

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“…LVH is a consequence of an increased cardiac myocyte size and myocardial fibrosis associated with augmented extracellular connective tissue and matrix metalloproteinase-2 (MMP-2) activity, activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and protein kinase C (PKC) pathways, abnormal Ca2+ homeostasis, mitochondrial dysfunction, oxidative stress, and apoptosis [ 18 , 19 , 20 , 21 , 22 ]. In such a context, neurohormonal dysfunction with overactivation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) plays a pivotal role in growth and hypertrophic signaling.…”

Section: Hypertension and Heart Failure Phenotypesmentioning

confidence: 99%

Hypertension and Heart Failure: From Pathophysiology to Treatment

Gallo,

Savoia

2024

IJMS

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Hypertension represents one of the primary and most common risk factors leading to the development of heart failure (HF) across the entire spectrum of left ventricular ejection fraction. A large body of evidence has demonstrated that adequate blood pressure (BP) control can reduce cardiovascular events, including the development of HF. Although the pathophysiological and epidemiological role of hypertension in the development of HF is well and largely known, some critical issues still deserve to be clarified, including BP targets, particularly in HF patients. Indeed, the management of hypertension in HF relies on the extrapolation of findings from high-risk hypertensive patients in the general population and not from specifically designed studies in HF populations. In patients with hypertension and HF with reduced ejection fraction (HFrEF), it is recommended to combine drugs with documented outcome benefits and BP-lowering effects. In patients with HF with preserved EF (HFpEF), a therapeutic strategy with all major antihypertensive drug classes is recommended. Besides commonly used antihypertensive drugs, different evidence suggests that other drugs recommended in HF for the beneficial effect on cardiovascular outcomes exert advantageous blood pressure-lowering actions. In this regard, type 2 sodium glucose transporter inhibitors (SGLT2i) have been shown to induce BP-lowering actions that favorably affect cardiac afterload, ventricular arterial coupling, cardiac efficiency, and cardiac reverse remodeling. More recently, it has been demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Other proposed agents, such as endothelin receptor antagonists, have provided contrasting results in the management of hypertension and HF. A novel, promising strategy could be represented by small interfering RNA, whose actions are under investigation in ongoing clinical trials.

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