Primary cilia are usually classified as non-motile organelles with microtubules arranged in “9 + 0” fashion. It has been suggested that, like the nucleus, mitochondria, golgi, and other intracellular organelles, a primary cilium can also be viewed as a separate entity within a cell () [21
]. A cilium can be studied as an organelle with five distinct domains: (1) the ciliary membrane
, a specialized domain composed of a protein and with a lipid composition different from that of the rest of the plasma membrane; (2) the soluble compartment
, also known as the matrix compartment or cilioplasm; (3) the axoneme
, composed of nine pairs of microtubules with a highly structured transport motor cytoskeleton; (4) ciliary tip
, housed specialized proteins whose roles are still to be explored further; (5) basal body
, a “mature” or “mother” centriole from which the primary cilium is projected.
Five distinct domains of a cilium.
As micro-sensory compartments, cilia have functions that depend on mechano-proteins such as polycystin-1 and polycystin-2 (). Thus, the overall functions of the sensory compartments depend on both functional and structural cilia proteins. Within a blood vessel, an abrupt increase in blood pressure or shear stress can be detected by these sensory proteins localized in the cilia [16
]. With cilium functioning as a local regulatory mechanism, the extracellular fluid mechanics can then be transduced and translated into a complex of intracellular signaling, which in turn would activate eNOS—an endothelial enzyme that synthesizes nitric oxide (NO) gas. In particular, shear stress-induced calcium and NO signaling has been reported in many endothelial cells [25
]. The released NO will diffuse from endothelial cells to the neighboring smooth muscle cells, thereby promoting vasodilation [26
]. The overall effects of cilia function are thus to decrease total peripheral resistance, therefore lowering the blood pressure.
Figure 1 Mechanosensory cilia as microcompartments. Primary cilia are mechanosensory compartments that house many sensory proteins. Activation of these compartments through the sensory machineries will generate a cascade of various proteins activation, which results (more ...)
The presence of primary cilia in vascular endothelia has been reported in human arteries [29
] and has been observed in cultured human cells [16
] and adult vascular system in vivo
]. Of particular interest is a high level of polycystin expression in endothelial cells, which is required for the structural integrity of blood vessels [39
]. The expression of polycystins in human endothelial cilia provides a critical link between cilia and the vasculature [16
]. Interestingly, the function of polycystin-1 as a mechanosensory molecule can be inactivated by proteolytic cleavage after exposure to high fluid-shear stress. This indicates that cilia function can also be regulated through modification of polycystin-1 via a high shear stress [24
]. This further suggests that in patients with high blood pressure, that is, high shear stress, cilia would very likely be unable to sense minute changes in blood pressure, which might result in failure to autoregulate the local circulatory system. This might increase the possibility of localized blood vessel injuries, such as aneurysm, atherosclerosis, dissection, edema, hemorrhage, and vascular ectasia, among others.
Throughout the cardiovascular system, patterns of fluid dynamics change considerably due to continuous vascular remodeling and patterning for microadaptation purposes [43
]. The changes in the fluid dynamics generate differential biomechanical forces. These forces can initiate a complex of gene expressions [5
] which may also alter cilia function or structure in endothelial cells [24
]. Consistent with this idea, it has been shown that not all vasculatures have cilia [38
]. Only arteries with low fluid shear or high fluid turbulence have cilia, particularly longer, well-developed cilia. Because prolonged exposure to high fluid-shear stress would induce cilia to disassemble [33
], it is possible that cilia may not be needed to sense high shear stress. Rather, endothelial cells may have other mechanisms, such as glycocalyx, to sense much higher mechanical forces [49