Desmin and Cardiac Disease: An Unfolding Story

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Cardiac output (CO), the amount of blood the heart pumps per minute, is a parameter in cardiovascular physiology determined by stroke volume and heart rate. Stroke volume, the amount of blood pushed from one of the ventricles per heartbeat, is influenced by preload, afterload, and contractility.
Preload
Preload refers to the initial elongation of the cardiac myocytes before contraction and is related to the volume of blood filling the heart at the end of diastole, or end-diastolic volume. The...

Cardiac Output
Cardiac output (CO) refers to the total amount of blood ejected by one of the ventricles in liters per minute (L/min). In a resting adult, CO ranges from 5 to 6 L/min, adjusting according to the body's metabolic requirements.
Effect of Heart Rate on Cardiac Output
Cardiac output adapts to metabolic demands during stress, physical activity, or illness. The autonomic nervous system regulates heart rate via the sinoatrial node. The parasympathetic nervous system decreases heart...

The heart beats rhythmically in a sequence called the cardiac cycle—a rapid coordination of contraction (systole) and relaxation (diastole).
The Process
Electrical signals—sent from the sinoatrial (SA) node in the right atrial wall to the atrioventricular (AV) node between the right atrium and right ventricle—cause both atria to simultaneously contract. When the signal reaches the AV node, it pauses for approximately a tenth of a second, allowing the atria to contract and...

The cardiac cycle refers to the sequence of events that occur in the heart from the beginning of one heartbeat to the next. It's characterized by alternating periods of contraction (systole) and relaxation (diastole) of the heart muscles.
During the cardiac cycle, blood flow through the heart is regulated entirely by changing pressure gradients. This sequence of events begins with the heart in a state of total relaxation, known as mid-to-late diastole, during which blood passively flows from...