Impact of co-morbidities on preconditioning signalling cascades in cardiovascular diseases: strategies for intervention.

Preconditioning has emerged as a promising approach in the management of ischaemic heart diseases. Ischaemic and pharmacological preconditioning have shown their ability to reduce myocardial infarct size and preserve cardiac function in various experimental and clinical settings. The underlying protective mechanisms of preconditioning involve the activation of signalling cascades that promote cell survival, inhibit cell damage and improve cellular energetics. However, the presence of cardiovascular co-morbidities such as ageing, diabetes, hyperlipidaemia, hypertension and chronic kidney disease is known to impair preconditioning stimuli and limit their effectiveness upon translation to clinical practice. This review discusses the impact of these co-morbidities on preconditioning signalling cascades and strategies to overcome this impairment by targeting comorbidity-specific pathways; using various preconditioning triggers, employing combined therapies and amplifying preconditioning stimuli. Additionally, bridging the gap between experimental and clinical studies through well-designed clinical trials is crucial for guaranteeing the feasibility and efficacy of preconditioning interventions in cardiovascular patients with diverse comorbidities.