The heart is a muscular organ whose primary function is to pump blood containing the oxygen and nutrients the body needs. Heart failure (HF) is a chronic, progressive condition in which the heart is not able to pump efficiently enough blood to meet the body’s demands. This could have been caused by heart attack, high blood pressure or lifestyle factors. Given that HF is a major cause of morbidity and mortality worldwide, there is a need for new treatments to reduce the number of costly hospitalizations and improve patients living conditions.
Initially, the heart unable to keep up body’s demands activates compensatory neurohormonal, molecular and cellular mechanisms to maintain an adequate performance. In this sense, there is an activation of two important systems, the renin-angiotensin-aldosterone (RAAS) and the sympathetic nervous systems (SNS), that lead the heart to undergo cardiac remodelling, involving changes in size, shape and structure. Primarily, the activation of these systems and heart remodelling exert a compensatory effect, thus, maintaining normal cardiac function. However, cardiac adaptation has its limits. Long-term SNS and RAAS stimulation of the heart leads to a progressive and irreversible dysfunction of the heart.
At this point, and to understand the progression of HF, we must focus on heart contraction and on its key regulator; calcium. Cardiac cell contraction is caused by a massive influx of calcium ions into the intracellular space. Then, calcium join contractile structures to allow cell contraction. Once this contraction has occurred, calcium is eliminated to ensure following contraction-relaxation cycles. In overload situations, the activation of the SNS and RASS systems allows a greater intracellular calcium concentration and, thus, a higher cell contraction. However, the chronic activation of these systems results in intracellular calcium collapse that deregulates the entire process of cell contraction-relaxation. Therefore, the progressive calcium deregulation causes cells to become dysfunctional and incapable to contract properly, leading to HF.
Based on foregoing, nowadays the strategies for HF treatment reside mostly on the inhibition of the SNS and the RAAS axes. Nevertheless, and despite the great clinical benefits obtained with these drugs, we still face certain limitations. In fact, the response to these drugs is not complete many patients continue to evolve towards HF.
In this context, and given that the stimulus that initiates the heart response is a mechanical overload, we are studying a type of channels embedded in cardiac cell membranes (mechanoreceptors) that respond to mechanical stimuli by allowing influx of calcium into the intracellular space. We hypothesize mechanoreceptor channels participate in HF, explaining the evolution of the disease even if SNS and RASS blockers are administered and that cardioselective inhibition of these channels may prevent the development of HF.